CASE STUDY

BRICKE INSTITUTE FOR HEALTH

INFECTIOUS DISEASES IN WEST AFRICA

A publication of Bricke International | 2009 REPORT

[INFECTIOUS DISEASES IN WEST AFRICA] CASE STUDY

This is a joint publication of the Center for Global Health and the public Engagement Unit of Bricke International and therefore its materials cannot be used without any prior permission from the management and staff of Bricke International or its subsidiaries. This report was sponsored by Athens Corporation, the main trustee of Bricke International and endorsed by the ACT NOW Center.

Signed ECHEFU BRIGHT IK. Bricke Institute for Global Health

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TABLE OF CONTENTS Preface Background and Rationale ANNEX 1 Overview and the Impact of Infectious Disease common in West Africa 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 1.10 1.11 1.12 Onchocerciasis (River Blindness) Syphilis Leishmaniasis (kala-azar) Lymphatic Filariasis (Elephantiasis) Hansen’s Disease (Leprosy) Malaria Tuberculosis Dengue Schistosomiasis (Bilharzias) HIV/AIDS Trachoma/Glaucoma and Cataract Vertigo Vaginal Fistula (VVF) 10 11 13 15 17 19 20 22 23 24 4 7

ANNEX 3 3.1 Administrative Details of Bricke International 3.2 Appreciation 3.3 Glossary

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PREFACE Mankind has been battling infectious diseases since the dawn of the species. Though there have been many victories over the centuries, this is a war not yet won. The health systems in sub-Saharan Africa face severe challenges in addressing infectious diseases and other healthcare needs. In addition to the lack of physical infrastructure and financial resources to provide adequate healthcare, countries are beset with a crippling shortage of trained healthcare workers. While sub-Saharan Africa which has 24% of the global disease burden, it has only 3% of the world healthcare workforce and accounts for less than 17% of the global healthcare spending. Of every 1000 babies born in the United Kingdom, five die before they reach their first birthday. In Mozambique, nearly 350 babies out of every 1000 die within a year. The death of any infant is a tragedy but why do forty times as many Mozambican families suffer this painful loss. In the UK, thanks to better hygiene, antibiotics and vaccines, infectious illnesses are a shadow of the threat they once were. In the developing countries, however, it’s a very different story. With limited global resources available to deal with the problem, where should we focus our efforts? Should we develop new drugs and vaccines to combat these diseases? Or would we be better off addressing underlying social, cultural, environmental and economic problems? Should the rich countries do more to help the poor ones? Or are there enough solutions ahead but not enough political will and cooperation to implement them. Bricke Institute for Global Health (BIGH) which is one of the major players in the Infectious Diseases advocacy initiatives believes that no government or organization could single handed tackle a problem as vast as Infectious Diseases in developing countries. But many different organizations including charities and pharmaceutical companies could make a vital impact in particular areas. The institute’s proposed World Health Initiative (WHI) christened the ACT NOW CAMPAIGN seeks to establish an International Public Private Partnership (IP3) for the control and eradication of eleven major Infectious Diseases within the next five years of the implementation of its 5-year strategic plan (2010-2014). IP3 will be a distinctive feature of the global health care landscape. One of the many advantages of the proposed IP3 is that it will mobilize partners with different even hostile philosophies around one common goal. IP3 makes it possible to share risks and responsibility and they embody the principle of ‘win-win’ solutions creating benefits for all parties. Pharmaceutical companies know they have guaranteed sales of new products perhaps also a subsidy from public or donor funds. Countries know they are getting high quality products at affordable prices. The pharmaceutical companies bring its unique skills and expertise to bear in developing new products and getting them through the regulatory approval process.

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WHI has come to believe that some of the set terrors in the limelight are caused by three diseases very much in the news: AIDS, TB and Malaria. Such attention for the big three infectious diseases is understandable. The consequences of the AIDS epidemic are so profound that they are now recognized as a threat to global security. Fuelled by the AIDS epidemic, TB has re-established itself often in its multidrug resistant form as a contagious and costly leading cause of death. TB’s return with a vengeance to wealthy nations shocked the world out of its complacent view that infectious diseases were a declining threat. Malaria stands out as probably the single most important impediment to socio economic development in endemic countries. It is deadly, firmly entrenched and inextricably linked to poverty. Malaria is also important to wealthy countries because it threatens the health of International travellers. Together, these three diseases cause over 700 Million episodes of illnesses and more than 20 Million deaths annually. Outbreaks of diseases are costly wherever and whenever they occur. However, outbreaks come to an end. The burden imposed by AIDS, TB and Malaria on economies in developing countries is enormous and constant. I believe that Malaria has powerfully shaped the global distribution of income and poverty. If the disease has been eliminated 35 years ago, up to $200 Billion could have been added to sub Saharan Africa’s current GDP of $300 Billion. Biological terror also comes in the form of so called neglected diseases, neglected because they do not affect wealthy nations, do not make headlines and do not interest the research community including the research based pharmaceutical industry. They cause great terror in their homeland but little international concern. The number of people incapacitated by these diseases is enormous. At the human level, the impact of the disease on development can be simply expressed. People who are sick cannot work or attend school. Malaria alone causes between 400 Million to 900 Million episodes of illnesses in African Children. High fever and febrile convulsions in infants and children can retard brain development with profound implications for societies. Schistosomiasis which infects 200 million people is also associated with impaired growth and development and poor school performance. For these and other neglected diseases, illness is not an episode like an outbreak that ends. If untreated, infection progresses to a point where disability is permanent. Blindness is the consequence of untreated Onchocerciasis and Trachoma. Severe heart disease develops in young people as a result of Chagas disease. Deformities associated with leprosy, leishmaniasis and lymphatic filariasis can become so severe that patients are cast out of the society as well as eliminated from the work force. The cost of medicines whether quality drugs or counterfeit can easily exceed the purchasing power of people living on less than $1 a day in countries where total annual health expenditure amounts to no more than $11 per person. For some of these diseases, money cannot buy an effective cure as none exists. For others, control tools are rapidly losing their effectiveness as antimicrobial resistance

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develops and spreads. The statistics are alarming and have been for quite some time. Conventional approaches have brought very little progress. Considerable hope now centres on our promise of IP3. Some academic observers believe that our idea of an efficient IP3 have the potential to transform the global public health landscape. It will bring major resources to bear on neglected diseases that affect large populations and can thus prove pivotal in fulfilling the moral obligation to improve the health status of poor people in low-income countries. The ACT NOW 5-Year strategic plan will focus primarily on key areas of infectious disease management which include: developing Rapid Diagnostic Test Kits (RDTK) for each of the eleven infectious diseases of interest, Drug Donation (and Production) Partnerships (D2P and DP2), Vaccine Development and Vector Control Initiative (VCI). We will build strong strategic alliances with government; pharmaceutical companies, Research institutions and the private sector in various World Health Initiatives that will ensure that new therapeutics are brought into the market. On the proposed WHI, our new headquarters shall have state of the art facilities and technology which will be at the disposal of our employees. This will challenge them to use their expertise and creativity as members of an interdisciplinary team. It is necessary to state that our philosophy is one of shared visions, goals, knowledge and performance. We believe this approach will bring shared success and ultimately shared value and hopefully, within the next 5-Years, we would have been able to achieve at least 80% of our shared goals.

Signed

EcheBriKefun
ECHEFU BRIGHT IKECHUKWU Chief Development Officer

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Background and Rationale Approximately 1 Billion people in the world are affected by neglected diseases. Most of them are poor and marginalized people living in rural parts of low income countries. Neglected diseases have received little attention and resources despite their magnitude and impact in both economic development and quality of life. They often result in lifelong disabilities and deformities and sometimes even cause deaths. One hundred years ago, the UK was plagued by infectious diseases. Victorians lived in fear of diseases such as TB, Cholera, Diphtheria and Scarlet fever. For us many of these names appear only in history text books, a reminder of how things used to be. Yet for much of the world’s population even though most of these diseases are preventable or treatable, they remain an ever present threat. With limited global resources available to deal with this problem, where should we focus our efforts? Should we develop new drugs and vaccines to combat these diseases? Or would we be better off addressing underlying social, cultural, environmental and economic problems? Should the rich do more to help the poor? Or are there enough solutions already but not enough political will and cooperation to implement them? Infectious Diseases have a disastrous economic impact on developing countries. As well as the cost of treating patients, the economy suffers because patients are not able to work. There are longer term consequences too. Some infectious Diseases such as hepatitis B virus can simmer into long term (chronic) conditions. Others such as malaria and Schistosomiasis may harm the physical and mental development of children who are especially vulnerable to infection. Many cancers are result of chronic infections.

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Making more medicines seems like a good idea but where might they come from? Muck of the technology and expertise needed to make medicines is to be found in pharmaceutical companies. Unfortunately, it’s not that simple. Most pharmaceutical companies are based in the developed countries which have different priorities such as cardiovascular diseases, diabetes and Alzheimer diseases. Pharmaceutical companies argue that they can survive and provide more therapies if they can make profit. Most of them are reluctant to invest vast amounts of time and money to developing drug that few could afford to buy. As a result, diseases caused by trypanosome (sleeping sickness and Chagas disease) and leprosy, have been dubbed neglected diseases because they attract so little investment. This can change when people from wealthy countries catch poor country diseases. The anti-malarial drug Mefloquine for example is a product of the United States army research stimulated by the impact of malaria on US soldiers during the Vietnam War. Tourism also ensures that there is still an important developing market for antimalarial. Similarly, leishmaniasis has bumped up the agenda when it was suggested as a possible cause of ill health in Gulf war veterans. However, even if pharmaceutical companies did adopt a neglected disease, the therapies will likelihood be too expensive for developing countries. And patent protection seen as essential to safeguard the pharmaceutical company’s high investment on drug development, prevents poor countries from making their own versions of medicines for many years. Developing new therapies or making existing therapies more accessible is one way of addressing the problem of infectious diseases in the developing countries. But would we be better of tackling other fundamental obstacles in health such as lifestyles, attitudes and poverty? Is HIV/AIDS more deserving than malaria? Should we be working on long term prospects or working out the best way to use what we already have? Should money spent on research actually be spent on treatment? Although, the focus is developing countries, this is a global issue. Are global trade agreements biased towards industrialized countries at the expense of developing countries? Does western aid come with too many strings attached? Are we imposing western values in countries with different cultures and traditions? The role of research also raises questions? What is the role of educative programs and what values do we put on deeply ingrained traditions and beliefs? How do we establish priorities? Clearly, there aren’t going to be easy answers to these questions and no easy cures to infectious diseases. The effect of poverty is the single biggest barrier to improving healthcare in developing countries. Until, people can reliably access nutritious food, clean water, healthcare facilities and trained medical staff, the vicious cycle of poverty-causing ill health and ill health-causing poverty will not be broken. Whatever approach is

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taken to improve healthcare, it needs to be innovative and provide real effects which will see to the successful eradication of most of these infectious diseases. It is necessary to state at this juncture that geography and climate has contributed in no small measure to the problem of infectious diseases in developing countries. The mosquitoes that transmit malaria parasites for example cannot survive in cold climates. Similarly, the parasitic disease Schistosomiasis has flourished largely because of the water snails that spread the parasite. Diseases also break out after floods or other environmental upheavals such as those caused by “El-Nino” (the Christ child), a periodic outbreak of bad weather at Christmas time linked to changes in ocean currents. When the horn of Africa was flooded in late 1997, it experienced upsurges of cholera, malaria and rift valley fever. Inevitably, it is the poor who suffers most. Subsistence farming is the bedrock of most developing societies and there is rarely money left for medicines. To make things worse, poor diets and malnutrition leave people less able to fight off infections. A further problem has been the huge increase in population movements. Migration from rural to urban areas and mass unrests means millions of people are living in overcrowded conditions in cities and refugee camps where infections can spread easily. In many developing countries, education about the causes and prevention of diseases could have very huge impact on health. But people may have very different ideas about what causes a disease. In Kenya for example, many villagers suffering from AIDS who start wasting away conclude they have Chira, an illness invited by breaking social rules and Mozambicans with the same symptoms may be suspected of avoiding cleansing rituals after a death. Better children’s education, including health education would have many benefits. Adult education such as the use of condoms to prevent sexually transmitted infections and HIV infections is another favoured option but presents many difficulties. In many countries, discussing issues such as sex or contraceptives is taboo, while religious groups may argue that promoting condom use encourages promiscuity or unnatural. The persistence of smoking in the UK shows just how hard it is to change people’s behaviour through health education. Others argue for greater empowerment of disadvantaged groups such as women. At present, many women in developing countries and in rich countries for that matter are afraid to say no to sex or to ask men to use a condom while they may feel there masculinity is compromised if their sexual freedom is challenged. Changing people’s attitudes is notoriously difficult. Furthermore, if a disease is likely to lead to social exclusion, it may be denied or hidden away offering more opportunity for it to spread. Also, medically correct approach may challenge deep-seated cultural traditions or personal view. Men

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may simply not accept that they have an infection like HIV, they cannot see. Sometimes, even whole countries are reluctant to acknowledge the problem, a factor that has undoubtedly encouraged the spread of AIDS. In South Africa which has the single biggest HIV infected population in the world, former president Thabo Mbeki long denied there was any link between AIDS and HIV. In September 2003, he reportedly told the Washington post, “Personally, I don’t know anybody who has died of AIDS”, sparking off angry reactions from South Africa people and AIDS activists who estimate that 600 South Africans die of AIDS daily. By contrast, Malawi’s president, Bakili Muluzi was widely applauded for publicly acknowledging that he had an HIV test. There are encouraging signs that recognizing the problem and taking concerted actions can make a difference. Uganda illustrates what can be achieved by acknowledging the problem early and making a real effort to change things. It has been able to half HIV infection levels in adults. But how much can health education really achieve with the everyday reality of poverty. The growth of densely populated cities with unsafe water and poor sanitation has created the perfect breeding ground for outbreaks of diseases. Looked at from this point of view, perhaps, it would be more productive to concentrate on providing improved sanitation, better housing, clean water and nutritious food rather than developing new pharmaceutical products. In developed countries, these relatively simple changes had a profound impact on people’s health in the 19th and 20th centuries. To treat patients effectively, doctors need to know what they are infected with. In the UK, that would involve a trip to the GP perhaps a sample being sent to a diagnostic laboratory or in complicated cases, referral to a specialist. Many developing countries however have no such healthcare infrastructure to call upon. Even knowing about symptoms may not be that helpful because many illnesses share similar features such as fever and febrile convulsions. There is this urgent need for simple, cheap and Rapid Diagnostic Tests (RDT) that could be used in rural locations without complicated equipment. As well as helping individual patients, accurate diagnosis and an understanding of how diseases are spread can suggest ways in which the cycle of infection can be broken. Prevention is better than cure and effective control strategies can save lives and money.

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ONCHOCERCIAIS BLINDNESS)

(RIVER

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ONCHOCERCIASIS IN WEST AFRICA
[INFECTIOUS DISEASES IN WEST AFRICA] CASE STUDY
This is a parasitic disease caused by a filarial worm that is transmitted to humans through the bites of Simulium black flies and endemic in more than 30 countries in Africa. Onchocerciasis also known as river blindness is the world's third leading infectious cause of blindness. Some 37 Million people are estimated to be infected and over 99% of those affected live in Africa. It is caused by Onchocerca volvulus, a nematode that can live for up to fifteen years in the human body. The worms spread throughout the body, and when they die, they cause intense itching and a strong immune system response that can destroy nearby tissue, such as the eye. Adult worms remain in subcutaneous nodules, limiting access to the host's immune system. Microfilarias, in contrast, are able to induce intense inflammatory responses, especially upon their death. Dying microfilaria have been recently discovered to release Wolbachia-derived antigens, triggering innate immune responses and producing the inflammation and its associated morbidity. Wolbachia species have been found to be endosymbionts of O. volvulus adults and microfilariae, and are thought to be the driving force behind most of O. volvulus morbidity. Severity of illness is directly proportional to the number of microfilaria and the power of the resultant inflammatory response. Skin involvement typically consists of intense itching, swelling, and inflammation. A grading System has been developed to categorize the degree of skin involvement: Acute Papular dermatitis - scattered pruritic papules; Chronic papular dermatitis larger papule, resulting in hyperpigmentation; Lichenified dermatitis hyperpigmented papules and plaques, with edema, lymphadenopathy, pruritus and common secondary bacterial infections; Skin atrophy - loss of elasticity, skin resembles tissue paper, 'lizard skin' appearance; Depigmentation - 'leopard skin' appearance, usually on anterior lower leg. Ocular involvement provides the common name associated with onchocerciasis, river blindness. The microfilariae migrate to the surface of the cornea. Punctate keratitis occurs in the infected area. This clears up as the inflammation subsides. However, if the infection is chronic, sclerosing keratitis can occur, making the affected area become opaque. Over time the entire cornea may become opaque, thus leading to blindness. There is some evidence to suggest that the effect on the cornea is caused by an immune response to bacteria present in the worms. The world Health Initiative on Onchocerciasis control WHICO meant to be launched in the 1st quarter of 2010 will be in two categories: developing a Rapid Diagnosis Test Kit (RDT) and the Ivermectin and Moxidectin Distrubution programs. Rapid Diagnostic Test Kits (RDT): Thanks to the development of the diethylcarbamazinecitrate (DEC) impregnated patch applied locally to the skin for the diagnosis of Onchocerca volvulus infection. This DEC patch which is meant to be distributed free to endemic areas under the WHICO program will be launched during the first quarter launch of WHICO. Clinical tests of the new patch indicate BRICKE INSTITUTE FOR GLOBAL HEALTH Page 14

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that it can provide a simple and non invasive surveillance tool for early detection of possible recrudescence of Onchocerciasis transmission and infection in an area where infection has been virtually eliminated and active control operations had been stopped. The patch involves a very small topical application of the drug DEC, a highly potent anti-onchocerciasis agent but not amenable for systemic use-to provoke a local reaction due to the killing of tiny oncho parasites present in the skin where the drug is applied topically. Control officers in Africa has devised a crude form of this tool by taking a small quantity of the drug in powder, mixing it with skin cream, applying it to a filter paper and then onto the skin for 24 hours. The presence of a small local skin reaction correlated with local killing of worms indicates an infection with Onchocerca volvulus. Treatment with Ivermectin: The drug Ivermectin (Mectizan) is the treatment for onchocerciasis; infected people can be treated once every twelve months. The drug paralyses the microfilariae and prevents them from causing itching. In addition, while the drug does not kill the adult worm, it does prevent them from producing additional offspring. The drug therefore prevents both morbidity and transmission. Additionally, Doxycycline can be added to the treatment regimen to kill the endosymbiotic bacteria, Wolbachia. This adjunct therapy has been shown to significantly lower microfilarial loads in the host and may have activity against the adult worms. WHICO will launch a Mectizan Donation and Distribution Program, MDDP in collaboration with Merck & Co. The MDP under the supervision of WHICO will work together with ministries of health and non-governmental development organizations such as the World Health Organization to provide free Mectizan to those who need it in endemic areas. Also, in collaboration with Wyeth Pharmaceuticals makers of Moxidectin, the Moxidectin Donation and Distribution Program (MDDP2) will be launched. The goal of this project is to set up a community-directed supply of Moxidectin for those who are infected.

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SYPHILIS IN WEST AFRICA

Syphilis is a sexually transmitted disease caused by the Spirochetal bacterium Treponema pallidum. The route of transmission of syphilis is almost always through sexual contact, although there are examples of congenital syphilis via transmission from mother to child in the uterus. The signs and symptoms of syphilis are numerous; before the advent of serological testing, precise diagnosis was very difficult. In fact, the disease was dubbed the "Great Imitator" because it was often confused with other diseases, particularly in its tertiary stage. Most persons with syphilis tend to be unaware of the infection and they can transmit the infection to sexual contacts or in the case of woman to her unborn child. If left untreated, syphilis can cause serious consequences such as still birth, prematurity and neonatal deaths. Adverse outcomes of pregnancies are preventable if the infection is detected and treated before mid-second trimester. Congenital syphilis kills more than 1 million babies a year worldwide but preventable if infected mothers are identified and treated appropriately as early as possible. World health Organization estimates that 12 million new cases of syphilis occur every year. In developing countries, 20-35% of women in child bearing age have syphilis. About 60% of pregnant women with syphilis will give birth to a dead baby and another 30% to live baby with congenital syphilis, a condition with mortality of up to 70%. The first well-recorded European outbreak of what is now known as syphilis occurred in 1494 when it broke out among French troops besieging Naples. The French may have caught it via Spanish mercenaries serving King Charles of France in that siege. From this centre, the disease swept across Europe. As Jared Diamond describes it, "When syphilis was first definitely recorded in Europe in 1495, its pustules often covered the body from the head to the knees, caused flesh to fall from people's faces, and led to death within a few months." In addition, the disease was more BRICKE INSTITUTE FOR GLOBAL HEALTH Page 16

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frequently fatal than it is today. Diamond concludes, "By 1546, the disease had evolved into the disease with the symptoms so well known to us today."The epidemiology of this first syphilis epidemic shows that the disease was either new or a mutated form of an earlier disease. Researchers concluded that syphilis was carried from the New World to Europe after Columbus' voyages. The findings suggested Europeans could have carried the nonvenereal tropical bacteria home, where the organisms may have mutated into a more deadly form in the different conditions and low immunity of the population of Europe. Syphilis was a major killer in Europe during the Renaissance. The world Health Initiative on Syphilis Control WHISC meant to be launched in the 1st quarter of 2010 will be in two categories: developing a Rapid Diagnosis Test Kit (RDT) and the treatment strategy. Rapid Diagnosis Test: It was only in the 20th century that effective tests and treatments for syphilis were developed. Microscopy of fluid from the primary or secondary lesion using dark field illumination is used to diagnose treponemal disease with high accuracy. The WHISC will be advocating the use of present-day syphilis screening tests, such as the Rapid Plasma Reagin (RPR) and Venereal Disease Research Laboratory (VDRL) tests which are cheap and fast but not completely specific, as many other conditions can cause a positive result. These tests are routinely used to screen blood donors. Notably, the spirochete that causes syphilis does not survive the conditions used to store blood and the number of transfusion transmitted cases of syphilis is minuscule, but the test is used to identify donors that might have contracted HIV from high risk sexual activity. The requirement to test for syphilis has been challenged due to the vast improvements in HIV testing. False positives on the rapid tests can be seen in viral infections (Epstein-Barr, hepatitis, varicella, measles), lymphoma, tuberculosis, malaria, Chagas Disease, endocarditis, connective tissue disease, pregnancy, intravenous drug abuse, or contamination. As a result, these two screening tests would be followed up by a more specific treponemal test. Tests based on monoclonal antibodies and immune fluorescence, including Treponema pallidum hemagglutination assay (TPHA) and Fluorescent Treponemal Antibody Absorption (FTA-ABS) are more specific and more expensive. Unfortunately, false positives can still occur in related treponomal infections such as yaws and pinta. Tests based on enzyme-linked immunosorbent assays, ELISA, are also used to confirm the results of simpler screening tests for syphilis. WHISC will diagnose Neuro syphilis by finding high numbers of leukocytes in the CSF or abnormally high protein concentration in the setting of syphilis infection. In addition, CSF would be tested with the VDRL test although some advocate using the FTA-ABS test to improve sensitivity. There is anecdotal evidence that the incidence of neuro syphilis is higher in HIV patients, and some have recommended that all HIVBRICKE INSTITUTE FOR GLOBAL HEALTH Page 17

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positive patients with syphilis should have a lumbar puncture to look for asymptomatic neuro syphilis. Treatment Options: WHISC believes the first-choice treatment for all manifestations of syphilis remains penicillin in the form of penicillin G. The effect of penicillin on syphilis was widely known before randomized clinical trials were used; as a result, treatment with penicillin is largely based on case series, expert opinion, and years of clinical experience. Parenteral penicillin G is the only therapy with documented effect during pregnancy. For early syphilis, one dose of penicillin is sufficient. Non-pregnant individuals who have severe allergic reactions to penicillin (e.g., anaphylaxis) will be effectively treated with oral tetracycline or doxycycline although data to support this is limited. Ceftriaxone may be considered as an alternative therapy, although the optimal dose is not yet defined. However, crossreactions in penicillin-allergic patients with cephalosporins such as ceftriaxone are possible. Azithromycin was suggested as an alternative. However, there have been reports of treatment failure due to resistance in some areas. If compliance and follow-up cannot be ensured, WHISC recommends desensitization with penicillin followed by penicillin treatment. All pregnant women with syphilis should be desensitized and treated with penicillin. Follow-up includes clinical evaluation at 1 to 2 weeks followed by clinical and serologic evaluation at 3, 6, 9, 12, and 24 months after treatment.

LEISHMANIASIS IN WEST AFRICA

Azithromycin has been used to treat syphilis in the past because of easy once-only dosing. However, in one study in San Francisco, azithromycin-resistance rates in syphilis, which were 0% in 2000, were 56% by 2004.

Leishmaniasis is a protozoan disease capable of causing a spectrum of clinical syndromes ranging from cutaneous ulcerations to systemic infections. With the exception of Australia, the Pacific Islands, and Antarctica, the parasites have been identified throughout large portions of the world. The protozoa are transmitted to mammals via the bite of the female sand fly of the genus Phlebotomus in the Old World and Lutzomyia in the New World. Humans are generally considered incidental hosts. For most species of Leishmania, an animal reservoir is required for endemic conditions to persist. Infections in wild animals are usually not pathogenic, with the exception of dogs, which may be severely affected. Traditionally divided between Old World and New World parasites, more than 20 pathogenic species have been identified. Common Old World hosts are domestic and feral dogs, rodents, foxes, jackals, wolves, raccoon-dogs, and hyraxes. Common New World hosts include sloths, anteaters, opossums, and rodents. Although uncommon in the United States, major epidemics currently exist in Afghanistan, Brazil, India, and Sudan. With the increase in international travel,

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immigration, overseas military exercises, and HIV co-infection, leishmaniasis is becoming more prevalent throughout the world. In the United States endemic leishmaniasis is uncommon. Periodic cases of localized cutaneous and diffuse cutaneous leishmaniasis have been reported in southern Texas and Oklahoma. The usual reservoir is the wood rat of the Southern Plains, but parasites have been identified in coyotes and domesticated dogs and cats. Spread by the sand fly vector Lutzomyia anthophora, cases are usually associated with exposure to the habitat of the wood rat. Travelers, government workers, and military personnel from the United States are at risk overseas. Since 2001, more than 700 US military personnel have been diagnosed with cutaneous leishmaniasis and 4 with visceral leishmaniasis after serving in Afghanistan and the Middle East. Up to 1% of US forces serving in the Southwest Asian Theater may have been infected. During the first Persian Gulf War, an estimated 400 cases of cutaneous leishmaniasis and 12 cases of viscerotropic leishmaniasis were reported. The etiological agent for most of these cutaneous leishmaniasis cases appears to have been Leishmania major. The Centers for Disease Control and Prevention (CDC) was notified of 129 cases between 1985 and 1990 involving travelers from the United States who acquired the disease abroad. During World War II, more than 1000 cases of cutaneous leishmaniasis were reported among US service members serving in the Persian Gulf. Illnesses now attributed to leishmaniasis have been identified throughout military campaigns from World War I back to antiquity. Leishmaniasis can be found in 88 countries in the intertropical and temperate regions of the world. Visceral leishmaniasis is endemic in 62 countries. The World Health Organization reports an annual incidence of 600,000 cases but estimates up to 1.5 million new cases of cutaneous leishmaniasis and 500,000 cases of visceral leishmaniasis occur each year. An estimated 12-million people are infected from a population of 350 million people who are at risk. Of these infections, approximately 25% are of visceral leishmaniasis, most of which come from the Indian subcontinent, Sudan, and Brazil. As of July 2005, an outbreak of a rapidly fatal form of visceral leishmaniasis in Ethiopia is causing concerns for an epidemic in the Horn of Africa. In contrast, most cases of localized cutaneous leishmaniasis come from Afghanistan, Saudi Arabia, Syria, Iran, and the Americas. In Kabul alone, an estimated 67,500 people are thought to be infected with cutaneous leishmaniasis. Old World leishmaniasis can be found in the Middle East, Indian subcontinent, Asia, Mediterranean, East Africa, and republics of the former Soviet Union. New World leishmaniasis exists throughout the Americas, with the exception of Canada, Chile, and Uruguay.

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Visceral and cutaneous leishmaniasis in patients with AIDS has been increasingly appreciated as a potential opportunistic infection. Co-infection with HIV has been reported in more than 35 countries throughout southern Europe, the Mediterranean Basin, Central and South America, and India. Disease occurs in conjunction with severe immunosuppression. The incidence of co-infection has decreased in developed countries because of the widespread use of anti-retroviral therapy. The world Health Initiative on Leishmaniasis (WHIL) will be launched in the 3rd quarter of 2010 along with WHIT. WHIL will be addressed along two categories: developing a Rapid Diagnosis Test Kit (RDT) and the treatment strategies (Drugs and Vaccine Development). Rapid Diagnosis: Leishmaniasis is diagnosed in the haematology laboratory by direct visualization of the amastigotes (Leishman-Donovan bodies). Buffy-coat preparations of peripheral blood or aspirates from marrow, spleen, lymph nodes or skin lesions should be spread on a slide to make a thin smear, and stained with Leishman's or Giemsa's stain (pH 7.2) for 20 minutes. Amastigotes are seen with monocytes or, less commonly in neutrophil in peripheral blood and in macrophages in aspirates. They are small, round bodies 2-4μm in diameter with indistinct cytoplasm, a nucleus and a small rod-shaped kinetoplast. Occasionally amastigotes may be seen lying free between cells. Treatment Strategies: There are two common therapies containing antimony (known as pentavalent antimonials), meglumine antimoniate (Glucantime) and sodium stibogluconate (Pentostam). It is not completely understood how these drugs act against the parasite; they may disrupt its energy production or trypanothione metabolism. Unfortunately, in many parts of the world, the parasite has become resistant to antimony and for visceral or mucocutaneous leishmaniasis, but the level of resistance varies according to species. Amphotericin is now the treatment of choice; failure of AmBisome to treat visceral leishmaniasis (Leishmania donovani) has been reported in Sudan, but this failure may be related to host factors such as coinfection with HIV or tuberculosis rather than parasite resistance. Miltefosine (Impavido), is a new drug for visceral and cutaneous leishmaniasis. The cure rate of miltefosine in phase III clinical trials is 95%; Studies in Ethiopia show that it is also effective in Africa. In HIV immunosuppressed people who are coinfected with leishmaniasis it has shown that even in resistant cases 2/3 of the people responded to this new treatment. Clinical trials in Colombia showed a high efficacy for cutaneous leishmaniasis. In mucocutaneous cases caused by L.brasiliensis it has shown to be more effective than other drugs. Miltefosine received approval by the Indian regulatory authorities in 2002 and in Germany in 2004. In 2005 it received the first approval for cutaneous leishmaniasis in Colombia. Miltefosine is also currently being investigated as treatment for mucocutaneous leishmaniasis caused by Leishmania braziliensis in Colombia, and preliminary results are very promising. It is now registered in many countries and is the first orally administered breakthrough BRICKE INSTITUTE FOR GLOBAL HEALTH Page 20

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therapy for visceral and cutaneous leishmaniasis. In October 2006 it received orphan drug status from the US Food and Drug administration. The drug is generally better tolerated than other drugs. Main side effects are gastrointestinal disturbance in the 1-2 days of treatment which does not affect the efficacy. Because it is available as an oral formulation, the expense and inconvenience of hospitalisation is avoided, which makes it an attractive alternative. Paromomycin is said to be an inexpensive (10 USD) and effective treatment for leishmaniasis. The Institute for OneWorld Health has developed paromomycin, results with which led to its approval as an orphan drug. The drug had originally been identified in the 1960's, but had been abandoned because it would not be profitable, as the disease mostly affects poor people. The Indian government approved paromomycin for sale in August 2006. Drug-resistant leishmaniasis may respond to immunotherapy (inoculation with parasite antigens plus an adjuvant) which aims to stimulate the body's own immune system to kill the parasite. Vaccines: Several potential vaccines are being developed, under pressure from the World Health Organization, but as of 2006 none is available. The team at the Laboratory for Organic Chemistry at the Swiss Federal Institute of Technology (ETH) in Zürich are trying to design a carbohydrate-based vaccine. The genome of the parasite Leishmania major has been sequenced, possibly allowing for identification of proteins that are used by the pathogen but not by humans; these proteins are potential targets for drug treatments. Currently there are no vaccines in routine use. However, the genomic sequence of Leishmania has provided a rich source of vaccine candidates. Genome-based approaches have been used to screen for novel vaccine candidates. One study screened 100 randomly selected genes as DNA vaccines against L. major infection in mice. Fourteen reproducibly protective novel vaccine candidates were identified.

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LYMPHATIC FILARIASIS IN WEST AFRICA
LYMPHATIC FILARIASIS (Elephantiasis) Elephantiasis destroys any semblance of a normal life for millions of people in developing countries. No matter how many times you see pictures of people with Lymphatic filariasis (LF) or see them sitting in a clinic, you don’t realize how this disease destroys lives until you see a patient trying to function in their own environment.” People with elephantiasis seem to disappear. They often don’t go outside because they are embarrassed. They may be ostracized by the community. They can’t wear shoes, and so they rarely attend church or any social activities. The disease is a global scourge—found in more than 80 countries, the highest prevalence in India and throughout sub-Saharan Africa. It is also found in the Americas, in places like Brazil, Guyana, Costa Rica, Haiti, and the Dominican Republic. LF was last seen on US soil in the 1930s near Charleston, South Carolina, and among soldiers returning from the South Pacific after World War II. The western world knows little about LF and its tremendous impact on the developing world. “It is a forgotten disease of forgotten people,” says Frank Richards, of the Rollins School of Public Health (RSPH). “But the numbers of people in the world suffering from this disease are staggering.” According to WHO, 120 million people suffer from LF, and another billion are at risk. After malaria, it is the second leading cause of permanent disability in the world. Grotesquely disfiguring and painful, LF is caused principally by the parasitic worm Wuchereria bancrofti. It is transmitted by mosquitoes that carry the parasite’s larvae from one person to the next. Children become infected when very young, although symptoms from damage to the lymphatic system usually do not appear until adulthood. Then fluid accumulates in arms, legs, breasts, and genitals, swelling them so massively they appear ready to burst. Skin thickens over time with hard, wood-like knobby growths resembling the hide of an elephant, giving the disease its common name—elephantiasis. In some villages, more than half of the males with LF suffer from hydrocoele—fluid-filled scrotums so swollen they can reach to the knees, making a normal social and sexual life impossible. Inefficient lymph glands leave patients vulnerable to bacterial infections in affected limbs, inflaming skin, lymph nodes, and lymphatic vessels, causing severe pain and fever. The physical symptoms of LF are indeed horrendous, but the economic and psychosocial impacts can be equally devastating. A disease of the poor, it undermines economic opportunity and destroys hope

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The economic burden of the disease is poorly defined, but the cost to India alone is estimated to be $150 billion. Although LF doesn’t kill patients outright, it often kills their ability to make a living and have a family. “In the past 10 years, public health authorities have come to look not only at deaths associated with a disease but at quality of life and disability as well,” says Richards. “LF robs people completely of their quality of life.” Although the parasite inflicts irreversible damages, LF is one of a handful of diseases possible to eradicate. New blood tests easily identify those infected but not yet sick from filarial infections, so preventive care can start early—good hygiene using soap and water, elevating affected limbs, and exercises can prevent painful acute episodes, secondary infections, and some swelling. We know LF can be eliminated because it’s been done before in some places. China did it beginning in the 1950s because the disease had such an impact on agricultural productivity. They treated 320 million people over 40 years, but they were successful. And although it was never prevalent here, LF went away by itself in places like South Carolina when communities improved sanitation and housing. We have an opportunity through this partnership to work with communities and industry, as well as government, financial, and nongovernmental organizations to make a real impact. This disease can be eradicated, and it will be—because it is the right thing to do. Medication has proven more effective than mosquito control in preventing infection by filarial worms. Recent breakthroughs that refined drug treatment regimens have helped make elimination of the disease possible. Drug company donations to developing countries make it affordable.

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HANSES DISEASE IN WEST AFRICA
HANSEN’S DISEASE (LEPROSY) Leprosy, also known as Hansen's disease, is an infectious disease caused by a bacterium called Mycobacterium leprae which causes disfiguration of the body or skin. The bacterium is an aerobic, acid fast, rod-shaped (bacillus) mycobacterium. The modern term for the disease is named after the discoverer of the bacterium, Gerhard Armauer Hansen . Historically, leprosy was an incurable and disfiguring disease. It is traditionally believed that lepers were shunned and sequestered in leper colonies. However, this is an over simplistic explanation not at all supported by historical evidence. A very great number of leprosaria or leper hospitals sprang up in the middle ages, particularly in England, and there were 250 in England by the 1230's, the first recorded one being at Harbledown. These institutions were run along monastic lines, and whilst lepers were encouraged to live in these monastic type establishments, this was more for the health of their own souls than for any segregation policy. Indeed, in Catholic tradition, those suffering from leprosy were considered to be going through Purgatory on Earth, and for this reason their suffering was considered more holy than the ordinary person. Saint Radegund was noted for washing the feet of lepers, and Orderic Vitalis writes of a monk, Ralf, who was so overcome by the plight of the leper that he prayed to catch leprosy himself (he eventually did catch it). The leper would carry a clapper and bell to warn of his approach, and this was as much to attract attention for charity as to warn people that a diseased person was near. Most importantly, Jesus was said to have walked with the leper, and so in Medieval religious society, it was a noble thing to be able to converse and build relationships with the leper. The disease is caused by a mycobacterium which multiplies very slowly (once every two weeks compared to other bacteria, which can multiply anywhere from daily to every 20 minutes) and mainly affects the skin, nerves, and mucous membranes. The organism has never been successfully grown in bacteriologic media or cell culture,

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and instead has been grown in mouse foot pads and more recently in nine-banded armadillos. It is related to M. tuberculosis, the mycobacterium that causes tuberculosis. The difficulty in culturing the organism appears to be due to the fact that the organism is an obligate intra-cellular parasite that lacks many necessary genes for independent survival. The complex and unique cell wall that makes the mycobacterium family difficult to destroy is apparently also the reason for the extremely slow replication rate. The mode of transmission of Hansen's disease remains uncertain. Most investigators think that M. leprae (also called "Hansen's bacillus") is usually spread from person to person in respiratory droplets. What is known is that the transmission rate is very low. In addition, approximately 95% of the population is naturally immune. Also, contrary to popular belief, Hansen's disease does not cause rotting of the flesh; however, due to the body's extensive attempts to rid itself of the bacterium, defenses such as inflammation, cytokines, activated macrophages and other mechanisms cause tissue destruction and regeneration leading to excessive growth and eventually mutilation. This chronic infectious disease usually affects the skin and peripheral nerves but has a wide range of possible clinical manifestations. Patients are classified as having paucibacillary (tuberculoid leprosy) or multibacillary Hansen's disease (lepromatous leprosy). Paucibacillary Hansen's disease is milder and characterized by one or more hypo pigmented skin macules. Multibacillary Hansen's disease is associated with symmetric skin lesions, nodules, plaques, thickened dermis, and frequent involvement of the nasal mucosa resulting in nasal congestion and epistaxis (nose bleeds). Other than humans, the only creatures known to be susceptible to leprosy are the armadillo, mangabey monkeys, rabbits, and mice (on their footpads). According to recent figures from the World Health Organization (WHO) new cases detected worldwide have decreased by approximately 107,000 cases or 21% from 2003 to 2004. This decreasing trend has been consistent for the past three years. In addition the "global registered prevalence" of leprosy was 286,063 cases with 407,791 new cases being detected during 2004. In 1999, the world incidence of Hansen's disease was estimated to be 640,000; and in 2000, 738,284 cases were identified. In 1999, 108 cases occurred in the United States. In 2000, the World Health Organization (WHO) listed 91 countries in which Hansen's disease is endemic, with India, Myanmar, and Nepal having 70% of cases. In 2002, 763,917 new cases were detected worldwide, and in that year the WHO listed Brazil, Madagascar, Mozambique, Tanzania and Nepal as having 90% of Hansen's disease cases.

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Worldwide, one to two million people are permanently disabled because of Hansen's disease. However, persons receiving antibiotic treatment or having completed treatment are considered free of active infection. India has the greatest number of leprosy cases, with Brazil second and Myanmar third. Hansen's disease is one of the infectious diseases tracked passively by the Centers for Disease Control and Prevention. Its prevalence in the United States has remained low and relatively stable. There are decreasing numbers of cases worldwide, though pockets of high prevalence continue in certain areas such as Brazil, South Asia (India, Nepal), some parts of Africa (Tanzania, Madagascar, Mozambique) and the western Pacific. Those having close contacts with patients with untreated, active, predominantly multibacillary disease, and persons living in countries with highly endemic disease are at risk of contracting the disease. Recent research suggests that there is genetic variation in susceptibility. The region of DNA responsible for this variability is also involved in Parkinson's disease, giving rise to current speculation that the two disorders may be linked in some way at the biochemical level. In addition, men are two times more likely to contract leprosy than women. In response to the incidence of dapsone resistance, the WHO introduced a multi drug regimen in 1981 that includes Rifampicin, dapsone and Clofazimine. Some clinical studies have also shown that certain quinolonees, minocycline and azithromycin have activity against M.leprae. The WHO recently recommended single dose treatment with rifampicin, minocycline or ofloxacin in patients with paucibacillary leprosy who have a simple skin lesion. However, the WHO still recommends the use of the long term multidrug regimens whenever possible because they have been found to be more efficacious.

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MALARIA IN WEST AFRICA
MALARIA Malaria is one of our pernicious enemies: a century's research, huge international efforts at eradicating and control and still it defies us. It is a life threatening parasitic disease transmitted from person to person through the bite of a female Anopheles mosquito. The clinical picture of severe malaria is dominated by three main problems: Anemia, respiratory distress and Coma. The most well known and feared manifestation of severe malaria is cerebral malaria in which the patient goes into coma and often convulsions. Malaria alone causes between 400 and 900 million episodes of illness in African children. High fevers and febrile convulsions in infants and children can retard brain development, with profound implications for societies. More than 2 Billion people (about 40% of the world's population) in 100 countries are at risk and there are at

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least 300 million cases of acute malaria each year. About 2.7 million people die of malaria each year, most of whom are children. Other high risk groups include, pregnant women, no-immune travelers, refugees, displaced persons or labour forces entering into endemic areas. Countries in topical Africa bear the brunt of malaria, accounting for more than 90% of the 300 million annual cases of malaria. Malaria has for several years been a major problem. Its economic impact in sub-Saharan Africa is staggering. Beyond the human toll (it kills 1 million people every year) (UN reports, 2004); every year Africa loses an estimated £12 billion in GDP as a result of the disease, Malaria diverts financial reserves into the purchase of drugs and insecticides, decreases income through sick leave and discourages foreign investment and tourism. It holds back and has a long term impact on their physical and mental development. 55 years ago, there was real optimism that malaria could be tamed. The insecticide DDT killed the mosquitoes that spread it, new powerful drugs were available to treat those infected. Surely, it was just a matter of time before it was eradicated. Sadly, it was a false dawn. The world grew concerned about the environmental impact of DDT while the powerful drugs gradually became less and less effective. Malaria was back with vengeance. The situation today is scarcely less bleak particularly in Africa. There is still no malaria vaccine and resistance to anti-malarial drugs is spreading alarmingly. There is one bright spot, however within the past two or three years, global partnerships have finished sequencing the DNA genomes of the three actors in the malaria drama: the malaria parasite, Plasmodium falciparum, the malaria transmitting mosquitoes, Anopheles gambiae and the human host. By themselves, the sequences are not much medical use. But they can greatly speed up research into the mechanisms of infection and disease. The development of drug resistance is a major concern in malaria treatment. The need to develop new drugs has never been greater. How can the parasite genome sequence help? One approach is to search for genes that are involved in the parasites internal biochemistry or its entry into the liver or red blood cells in which it lives. The idea is to find a vital part of the infection process or a vulnerable point in the parasites metabolism then to find drugs that block entry of the parasite or cripple its cellular biochemistry. Good targets are enzymes that are essential for parasite survival but are not present in humans and proteins the parasite used to grip into the cells it invades. Thanks to these approaches, several promising drugs are now under development.

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The world Health Initiative on Malaria (WHIM) will be launched in the 3rd quarter of 2010 along with WHIT and WHIL. WHIM will be addressed along two categories: Insecticide Treated Nets and Drugs. Insecticide Treated Nets (ITNs): ITNs are a core intervention to the WHIM program. They are used to prevent infection and disease especially among high risk groups such as children under the age of 5 years and pregnant women. Controlled trials of ITNs show that mortality in children less than 5 years of age can be reduced by 17% with high coverage of this intervention. ITNs are a highly cost effective means of preventing malaria with cost effectiveness ranges falling into the attractive (cost per disability Adjusted Life Year, DALY, averted below $150) or highly attractive cost per DALY averted below $25-$30 WHIM having understood the efficacy and effectiveness of ITNs in mosquito control will launch through an efficient IP3 in collaboration with Bayer environmental Science formulators of the K-O Tab 1-2-3 which is a retreatment chemical popularly called DIP-IT-YOURSELF insecticide retreatment kits. The formulation has been found effective on polyester nets in wash trials. Another key innovation are long lasting individual nets (LLIN) defined as a net which gives greater than 80% mortality in 3 minuites exposure bioassays after 20 standardized washes. So far there are two LLINs models in the market the BIGH would be investing in over the next 5 years. They are: Olyset TM produced in China and Tanzania made out of wide meshed high density polyethylene in which the insecticide (permethrin) is incorporated directly into the fiber (approximate retail price is $7) and PermaNet TM produced in Vietnam which is a polyester mosquito net impregnated with deltamethrin during manufacture approximate retail price $4). Drugs: The main obstacle to effective malaria treatment is the emergence of drug resistance strains of Plasmodium falciparum. Parasite resistance to chloroquine and other antimalarial drugs such as sulfadoxine-pyrimethamine and amodiaquine has increased steadily in recent years in many malaria endemic countries. ACTS that combine artemisinin derivative with another antimalarial such as lumefantrine or amordiaquine promise both increased efficacy and reduced rate of development of resistance. One drug that holds a lot of promise is Novartis Artemetherlumefantrine (coartem) (4 tablets twice daily for 3 days for an adult). The WHIM hopefully would sign a pact with Novartis to make coartem available through Bricke International for use in the public sector of malaria endemic countries.

TUBERCULOSIS

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Tuberculosis (abbreviated as TB for tubercle bacillus or Tuberculosis) is a common and often deadly infectious disease caused by mycobacteria, in humans mainly Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs (as pulmonary TB) but can also affect the central nervous system, the lymphatic system, the circulatory system, the genitourinary system, the gastrointestinal system, bones, joints, and even the skin. Other mycobacteria such as Mycobacterium bovis, Mycobacterium africanum, Mycobacterium canetti, and Mycobacterium microti also cause tuberculosis, but these species are less common in humans. The classic symptoms of tuberculosis are a chronic cough with blood-tinged sputum, fever, night sweats, and weight loss. Infection of other organs causes a wide range of symptoms. The diagnosis relies on radiology (commonly chest X-rays), a tuberculin skin test, blood tests, as well as microscopic examination and microbiological culture of bodily fluids. Tuberculosis treatment is difficult and requires long courses of multiple antibiotics. Contacts are also screened and treated if necessary. Antibiotic resistance is a growing problem in (extensively) multi-drug-resistant tuberculosis. Prevention relies on screening programs and vaccination, usually with Bacillus Calmette-Guérin (BCG vaccine). Tuberculosis is spread through the air, when people who have the disease cough, sneeze, or spit. One–third of the world's current population has been infected with M. tuberculosis, and new infections occur at a rate of one per second. However, most of these cases will not develop the full-blown disease; asymptomatic, latent infection is most common. About one in ten of these latent infections will eventually progress to active disease, which, if left untreated, kills more than half of its victims. The proportion of people in the general population who become sick with tuberculosis each year is stable or falling worldwide but, because of population growth, the absolute number of new cases is still increasing. In 2004, mortality and morbidity statistics included 14.6 million chronic active cases, 8.9 million new cases, and 1.6 million deaths, mostly in developing countries. In addition, a rising number of people in the developed world are contracting tuberculosis because their immune systems are compromised by immunosuppressive drugs, substance abuse, or AIDS. The distribution of tuberculosis is not uniform across the globe with about 80% of the population in many Asian and African countries testing positive in tuberculin tests, while only 5-10% of the US population test positive. It is estimated that the US has 25,000 new cases of tuberculosis each year, 40% of which occur in immigrants from countries where tuberculosis is endemic. The world Health Initiative on Tuberculosis WHIT meant to be launched in the 3rd quarter of 2010 will be in four categories: developing a Rapid Diagnosis Test Kit (RDT), DOTS and the treatment strategies (Drugs and Vaccine Development). Rapid Diagnosis: The Mantoux Tuberculin Skin Test is a viable test for TB. Tuberculosis is diagnosed definitively by identifying the causative organism (Mycobacterium tuberculosis) in a clinical sample (for example, sputum or pus). When this is not BRICKE INSTITUTE FOR GLOBAL HEALTH Page 31

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possible, a probable diagnosis may be made using imaging (X-rays or scans) and/or a tuberculin skin test. The main problem with tuberculosis diagnosis is the difficulty in culturing this slowgrowing organism in the laboratory (it may take 4 to 12 weeks for blood or sputum culture). A complete medical evaluation for TB includes a medical history, a physical examination, a chest X-ray, microbiological smears and cultures. It may also include a tuberculin skin test, a serological test. The interpretation of the tuberculin skin test depends upon the person's risk factors for infection and progression to TB disease, such as exposure to other cases of TB or immune-suppression. Currently, latent infection is diagnosed in a non-immunized person by the Tuberculin Skin Test, which yields a delayed hypersensitivity type response to an extract made from M. tuberculosis. Those immunized for TB or with past-cleared infection will respond with delayed hypersensitivity parallel to those currently in a state of infection, so the test must be used with caution, particularly with regard to persons from countries where TB immunization is common. Tuberculin tests have the disadvantage in that they may produce false negatives, especially when the patient is co-morbid with sarcoidosis, Hodgkins lymphoma, malnutrition, or most notably active tuberculosis disease. New TB tests are being developed that offer the hope of cheap, fast and more accurate TB testing. These include polymerase chain reaction detection of bacterial DNA, and assays to detect the release of interferon gamma in response to mycobacterial proteins such as ESAT-6. These are not affected by immunization or environmental mycobacteria, so generate fewer false positive results. The development of a rapid and inexpensive diagnostic test would be particularly valuable in the developing world. Monitoring and DOTS: DOTS stands for "Directly Observed Therapy, Short-course" and is a major plank in the WHO global TB eradication programme. The DOTS strategy focuses on five main points of action. These include government commitment to control TB, diagnosis based on sputum-smear microscopy tests done on patients who actively report TB symptoms, direct observation short-course chemotherapy treatments, a definite supply of drugs, and standardized reporting and recording of cases and treatment outcomes. The WHO advises that all TB patients should have at least the first two months of their therapy observed (and preferably the whole of it observed): this means an independent observer watching tuberculosis patients swallow their anti-TB therapy. The independent observer is often not a healthcare worker and may be a shopkeeper or a tribal elder or similar senior person within that society. DOTS is used with intermittent dosing (thrice weekly or 2HREZ/4HR3). Twice weekly dosing is effective but not recommended by the WHO, because there is no margin for error (accidentally omitting one dose per week results in once weekly dosing, which is ineffective). Treatment with properly implemented DOTS has a success rate exceeding 95% and prevents the emergence of further multi-drug resistant strains of tuberculosis. BRICKE INSTITUTE FOR GLOBAL HEALTH Page 32

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Administering DOTS, decreases the possibilities of tuberculosis from recurring, resulting in a reduction in unsuccessful treatments. This is in part due to the fact that areas without the DOTS strategy generally provide lower standards of care. Areas with DOTS administration help lower the number of patients seeking help from other facilities where they are treated with unknown treatments resulting in unknown outcomes. However if the DOTS program is not implemented or done so incorrectly positive results will be unlikely. In order for the program to work efficiently and accurately health providers must be fully engaged, links must be built between public and private practitioners, health services must be available to all, and global support is provided to countries trying to reach their TB prevention, and treatment aims. Some researchers suggest that, because the DOTS framework has been so successful in the treatment of tuberculosis in sub-Saharan Africa, DOTS should be expanded to non-communicable diseases such as diabetes mellitus, hypertension, and epilepsy. Self-administered therapy (SAT), is another form of treatment for tuberculosis, however it does not have a reliable efficiency rate. Patients receiving SAT are known to be negligent in completing their treatment programs, resulting in relapses. Some people recommend monthly surveillance until cultures converts to negative; this does not form any part of the UK or WHO recommendations for TB. If cultures are positive or symptoms do not resolve after three months of treatment, it is necessary to re-evaluate the patient for drug-resistant disease or non adherence to drug regimen. If cultures do not convert to negative despite three months of therapy, consider initiating directly observed therapy. Tuberculosis Treatment: Treatment for TB uses antibiotics to kill the bacteria. The two antibiotics most commonly used are rifampicin and isoniazid. However, instead of the short course of antibiotics typically used to cure other bacterial infections, TB requires much longer periods of treatment (around 6 to 12 months) to entirely eliminate mycobacteria from the body. Latent TB treatment usually uses a single antibiotic, while active TB disease is best treated with combinations of several antibiotics, to reduce the risk of the bacteria developing antibiotic resistance. People with latent infections are treated to prevent them from progressing to active TB disease later in life. However, treatment using Rifampicin and Pyrazinamide is not risk-free. The Centers for Disease Control and Prevention (CDC) notified healthcare professionals of revised recommendations against the use of rifampin plus pyrazinamide for treatment of latent tuberculosis infection, due to high rates of hospitalization and death from liver injury associated with the combined use of these drugs. Drug resistant tuberculosis is transmitted in the same way as regular TB. Primary resistance occurs in persons who are infected with a resistant strain of TB. A patient with fully-susceptible TB develops secondary resistance (acquired resistance) during TB therapy because of inadequate treatment, not taking the prescribed regimen BRICKE INSTITUTE FOR GLOBAL HEALTH Page 33

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appropriately, or using low quality medication. Drug-resistant TB is a public health issue in many developing countries, as treatment is longer and requires more expensive drugs. Multi-drug-resistant tuberculosis (MDR-TB) is defined as resistance to the two most effective first-line TB drugs: rifampicin and isoniazid. Extensively drugresistant TB (XDR-TB) is also resistant to three or more of the six classes of second-line drugs. Vaccines: Many countries use Bacillus Calmette-Guérin (BCG) vaccine as part of their TB control programs, especially for infants. According to the W.H.O., this is the most often used vaccine worldwide, with 85% of infants in 172 countries immunized in 1993.This was the first vaccine for TB and developed at the Pasteur Institute in France between 1905 and 1921. However, mass vaccination with BCG did not start until after World War II. The protective efficacy of BCG for preventing serious forms of TB (e.g. meningitis) in children is greater than 80%; its protective efficacy for preventing pulmonary TB in adolescents and adults is variable, ranging from 0 to 80%. In South Africa, the country with the highest prevalence of TB, under the WHIT, BCG will be given to all children under age three. However, BCG is less effective in areas where mycobacteria are less prevalent; therefore BCG will not be given to the entire population in these countries. In the USA, for example, BCG vaccine is not recommended except for people who meet specific criteria: Infants or children with negative skin test results who are continually exposed to untreated or ineffectively treated patients or will be continually exposed to multidrug-resistant TB; Healthcare workers considered on an individual basis in settings in which a high percentage of MDR-TB patients has been found, transmission of MDR-TB is likely, and TB control precautions have been implemented and were not successful. BCG provides some protection against severe forms of pediatric TB, but has been shown to be unreliable against adult pulmonary TB, which accounts for most of the disease burden worldwide. Currently, there are more cases of TB on the planet than at any other time in history and most agree there is an urgent need for a newer, more effective vaccine that would prevent all forms of TB—including drug resistant strains—in all age groups and among people with HIV. Several new vaccines to prevent TB infection are being developed. The first recombinant tuberculosis vaccine rBCG30, entered clinical trials in the United States in 2004, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). A 2005 study showed that a DNA TB vaccine given with conventional chemotherapy can accelerate the disappearance of bacteria as well as protect against reinfection in mice; it may take four to five years to be available in humans. A very promising TB vaccine, MVA85A, is currently in phase II trials in South Africa by a group led by Oxford University, and is based on a genetically modified vaccinia virus. Many other strategies are also being used to develop novel vaccines, including both subunit vaccines (fusion molecules composed of two recombinant proteins BRICKE INSTITUTE FOR GLOBAL HEALTH Page 34

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delivered in an adjuvant) such as Hybrid-1, HyVac4 or M72, and recombinant adenoviruses such as Ad35. Some of these vaccines can be effectively administered without needles, making them preferable for areas where HIV is very common. All of these vaccines have been successfully tested in humans and are now in extended testing in TB-endemic regions. In order to encourage further discovery, WHIT is promoting new economic models of vaccine development including prices, tax incentives and advance market commitments.

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DENGUE FEVER
DENGUE FEVER Dengue fever and dengue hemorrhagic fever (DHF) are acute febrile diseases, found in the tropics, and caused by four closely related virus serotypes of the genus Flavivirus, family Flaviviridae. It is also known as breakbone fever. The geographical spread includes northern Australia and northern Argentina, and the entire Singapore, Malaysia, Taiwan, Thailand, Vietnam, Indonesia, Honduras, Costa Rica, Philippines, Pakistan, India, Bangladesh, Mexico, Suriname, Puerto Rico, Bolivia, Brazil, Guyana, Venezuela, Barbados, Trinidad and Samoa. Unlike malaria, dengue is just as prevalent in the urban districts of its range as in rural areas. Each serotype is sufficiently different that there is no cross-protection and epidemics caused by multiple serotypes (hyper-endemicity) can occur. Dengue is transmitted to humans by the Aedes aegypti or more rarely the Aedes albopictus mosquito, which feed during the day. The WHO says some 2.5 billion people, two fifths of the world's population, are now at risk from dengue and estimates that there may be 50 million cases of dengue infection worldwide every year. The disease is now epidemic in more than 100 countries. The disease manifests as a sudden onset of severe headache, muscle and joint pains (myalgias and arthralgias—severe pain that gives it the nick-name break-bone fever or bone crusher disease), fever, and rash. The dengue rash is characteristically BRICKE INSTITUTE FOR GLOBAL HEALTH Page 36

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bright red petechiae and usually appears first on the lower limbs and the chest; in some patients, it spreads to cover most of the body. There may also be gastritis with some combination of associated abdominal pain, nausea, vomiting, or diarrhea. Some cases develop much milder symptoms which can be misdiagnosed as influenza or other viral infection when no rash is present. Thus travelers from tropical areas may pass on dengue in their home countries inadvertently, having not been properly diagnosed at the height of their illness. Patients with dengue can pass on the infection only through mosquitoes or blood products and only while they are still febrile. The classic dengue fever lasts about six to seven days, with a smaller peak of fever at the trailing end of the disease (the so-called biphasic pattern). Clinically, the platelet count will drop until the patient's temperature is normal. Cases of DHF also show higher fever, variable haemorrhagic phenomena, thrombocytopenia, and haemo-concentration. A small proportion of cases lead to dengue shock syndrome (DSS) which has a high mortality rate. DHF combined with a cirrhotic liver has been suspected in rapid development of hepatocellular carcinoma (HCC). Given that the Dengue virus (DEN) is related to the Hepatitis C virus, this is an avenue for further research as HCC is among the top five cancerous causes of death outside Europe and North America. Normally HCC does not occur in a cirrhotic liver for ten or more years after the cessation of the poisoning agent. DHF patients can develop HCC within one year of cessation of abuse. The world Health Initiative on Dengue (WHID) will be launched in the 3rd quarter of 2010 along with WHIT and WHIL. WHID will be addressed along two categories: developing a Rapid Diagnosis Test Kit (RDT) and the treatment strategies (Drugs and Vaccine Development). Rapid Diagnosis: The diagnosis of dengue is usually made clinically. The classic picture is high fever with no localising source of infection, a petechial rash with thrombocytopenia and relative leukopenia - low platelet and white blood cell count. Care has to be taken as diagnosis of DHF can mask end stage liver disease and vice versa. Serology and polymerase chain reaction (PCR) studies are available to confirm the diagnosis of dengue if clinically indicated. Treatment Strategies: The mainstay of treatment is timely supportive therapy to tackle shock due to haemo concentration and bleeding. Close monitoring of vital signs in critical period (between day 2 to day 7 of fever) is vital. Increased oral fluid intake is recommended to prevent dehydration. Supplementation with intravenous fluids may be necessary to prevent dehydration and significant concentration of the blood if the patient is unable to maintain oral intake. A platelet transfusion is indicated in rare cases if the platelet level drops significantly (below 20,000) or if there is significant bleeding. The presence of melena may indicate internal gastrointestinal bleeding requiring platelet and/or red blood cell transfusion.

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Emerging Treatments: Emerging evidence suggests that mycophenolic acid and ribavirin inhibit dengue replication. Initial experiments showed a fivefold increase in defective viral RNA production by cells treated with each drug. In vivo studies, however, have not yet been done. Unlike HIV therapy, lack of adequate global interest and funding greatly hampers the development of treatment regime.

SCHISTOSOMIASIS
SCHISTOSOMIASIS Schistosomiasis (also known as bilharzia, bilharziosis or snail fever) is a parasitic disease caused by several species of fluke of the genus Schistosoma. Although it has a low mortality rate, schistosomiasis often is a chronic illness that can damage internal organs and, in children, impair growth and cognitive development. The urinary form of schistosomiasis is associated with increased risks for bladder cancer in adults. Schistosomiasis is the second most socioeconomically devastating parasitic disease after malaria. This disease is most commonly found in Asia, Africa, and South America, especially in areas where the water contains numerous freshwater snails, which may carry the parasite. The disease is found in tropical countries in Africa, Caribbean, eastern South America, south east Asia and in the Middle East. Schistosoma mansoni is found in BRICKE INSTITUTE FOR GLOBAL HEALTH Page 38

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parts of South America and the Caribbean, Africa, and the Middle East; S. haematobium in Africa and the Middle East; and S. japonicum in the Far East. S. mekongi and S. intercalatum are found focally in Southeast Asia and central West Africa, respectively. The disease is endemic to 74 countries, affecting an estimated 200 million people, half of whom live in Africa. A few countries have eradicated the disease, and many more are working toward it. The World Health Organization is promoting these efforts. In some cases, urbanization, pollution, and/or consequent destruction of snail habitat has reduced exposure, with a subsequent decrease in new infections. The most common way of getting Schistosomiasis in developing countries is by wading or swimming in lakes, ponds and other bodies of water which are infested with the snails (usually of the Biomphalaria, Bulinus, or Oncomelania genus) that are the natural reservoirs of the Schistosoma pathogen. Above all, schistosomiasis is a chronic disease. Many infections are subclinically symptomatic, with mild anemia and malnutrition being common in endemic areas. Acute schistosomiasis (Katayama's fever) may occur weeks after the initial infection, especially by S. mansoni and S. japonicum. Manifestations include: Abdominal pain ,cough , Diarrhea, Eosinophilia - extremely high eosinophil granulocyte count, Fever, Fatigue, Hepatosplenomegaly - the enlargement of both the liver and the spleen. Occasionally central nervous system lesions occur: cerebral granulomatous disease may be caused by ectopic S. japonicum eggs in the brain, and granulomatous lesions around ectopic eggs in the spinal cord from S. mansoni and S. haematobium infections may result in a transverse myelitis with flaccid paraplegia. Continuing infection may cause granulomatous reactions and fibrosis in the affected organs, which may result in manifestations that include: Colonic polyposis with bloody diarrhea (Schistosoma mansoni mostly); Portal hypertension with hematemesis and splenomegaly (S. mansoni, S. japonicum); Cystitis and ureteritis (S. haematobium) with hematuria, which can progress to bladder cancer; Pulmonary hypertension (S. mansoni, S. japonicum, more rarely S. haematobium); Glomerulonephritis; and central nervous system lesions. The world Health Initiative on Dengue (WHID) will be launched in the 3rd quarter of 2010 along with WHIT and WHIL. WHID will be addressed along two categories: developing a Rapid Diagnosis Test Kit (RDT) and the treatment strategies (Drugs and Vaccine Development) and Vector Control. Laboratory diagnosis: Microscopic identification of eggs in stool or urine is the most practical method for diagnosis. The stool exam is the more common of the two. For the measurement of eggs in the feces of presenting patients the scientific unit used is epg or eggs per gram. Stool examination is performed when infection with S.

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mansoni or S. japonicum is suspected, and urine examination should be performed if S. haematobium is suspected. Eggs can be present in the stool in infections with all Schistosoma species. The examination can be performed on a simple smear (1 to 2 mg of fecal material). Since eggs may be passed intermittently or in small amounts, their detection will be enhanced by repeated examinations and/or concentration procedures (such as the formalin-ethyl acetate technique). In addition, for field surveys and investigational purposes, the egg output can be quantified by using the Kato-Katz technique (20 to 50 mg of fecal material) or the Ritchie technique. Eggs can be found in the urine in infections with S. japonicum and with S. intercalatum (recommended time for collection: between noon and 3 PM). Detection will be enhanced by centrifugation and examination of the sediment. Quantification is possible by using filtration through a nucleopore membrane of a standard volume of urine followed by egg counts on the membrane. Investigation of S. haematobium should also include a pelvic x-ray as bladder wall calcificaition is highly characteristic of chronic infection. Treatment Strategies: Schistosomiasis is readily treated using a single oral dose of the drug Praziquantel annually. WHIS will launch a partnership with MedPharm for the donation and distribution of Praziquantel. As with other major parasitic diseases, there is ongoing and extensive research into developing a schistosomiasis vaccine that will prevent the parasite from completing its life cycle in humans. Antimony has been used in the past to treat the disease. In low doses, this toxic metalloid bonds to sulfur atoms in enzymes used by the parasite and kills it without harming the host. This treatment is not referred to in present-day peer-review scholarship; Praziquantel is universally used. Outside of the US, there is a second drug available for treating Schistosoma mansoni (exclusively) called Oxamniquine. Eliminating or avoiding the snails: Prevention is best accomplished by eliminating the water-dwelling snails which are the natural reservoir of the disease. Acrolein, copper sulfate, and niclosamide can be used for this purpose. Recent studies have suggested that snail populations can be controlled by the introduction or augmentation of existing crayfish populations; as with all ecological interventions, however, this technique must be approached with caution.

HIV/AIDS IN WEST AFRICA

HIV/AIDS

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Acquired immune deficiency syndrome or acquired immunodeficiency syndrome (AIDS) is a disease of the human immune system caused by the Human immunodeficiency virus (HIV). This condition progressively reduces the effectiveness of the immune system and leaves individuals susceptible to opportunistic infections and tumors. HIV is transmitted through direct contact of a mucous membrane or the bloodstream with a bodily fluid containing HIV, such as blood, semen, vaginal fluid, pre-seminal fluid, and breast milk. This transmission can involve anal, vaginal or oral sex, blood transfusion, contaminated hypodermic needles, exchange between mother and baby during pregnancy, childbirth, or breastfeeding, or other exposure to one of the above bodily fluids. AIDS is now a pandemic. In 2007, it was estimated that 33.2 million people lived with the disease worldwide, and that AIDS had killed an estimated 2.1 million people, including 330,000 children. Over three-quarters of these deaths occurred in subSaharan Africa, retarding economic growth and destroying human capital. Genetic research indicates that HIV originated in west-central Africa during the late nineteenth or early twentieth century. AIDS was first recognized by the U.S. Centers for Disease Control and Prevention in 1981 and its cause, HIV, identified in the early 1980s. Although treatments for AIDS and HIV can slow the course of the disease, there is currently no vaccine or cure. Antiretroviral treatment reduces both the mortality and the morbidity of HIV infection, but these drugs are expensive and routine access to antiretroviral medication is not available in all countries. Due to the difficulty in treating HIV infection, preventing infection is a key aim in controlling the AIDS epidemic, with health organizations promoting safe sex and needle-exchange programmes in attempts to slow the spread of the virus. The symptoms of AIDS are primarily the result of conditions that do not normally develop in individuals with healthy immune systems. Most of these conditions are infections caused by bacteria, viruses, fungi and parasites that are normally controlled by the elements of the immune system that HIV damages. Opportunistic infections are common in people with AIDS. HIV affects nearly every organ system. People with AIDS also have an increased risk of developing various cancers such as Kaposi's sarcoma, cervical cancer and cancers of the immune system known as lymphomas. Additionally, people with AIDS often have systemic symptoms of infection like fevers, sweats (particularly at night), swollen glands, chills, weakness, and weight loss. The specific opportunistic infections that AIDS patients develop BRICKE INSTITUTE FOR GLOBAL HEALTH Page 41

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depend in part on the prevalence of these infections in the geographic area in which the patient lives. Patients with HIV infection have substantially increased incidence of several cancers. This is primarily due to co-infection with an oncogenic DNA virus, especially Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpes virus (KSHV), and human papilloma virus (HPV). Kaposi's sarcoma (KS) is the most common tumor in HIV-infected patients. The appearance of this tumor in young homosexual men in 1981 was one of the first signals of the AIDS epidemic. Caused by a gamma herpes virus called Kaposi's sarcoma-associated herpes virus (KSHV), it often appears as purplish nodules on the skin, but can affect other organs, especially the mouth, gastrointestinal tract, and lungs. High-grade B cell lymphomas such as Burkitt's lymphoma, Burkitt's-like lymphoma, diffuse large B-cell lymphoma (DLBCL), and primary central nervous system lymphoma present more often in HIV-infected patients. These particular cancers often foreshadow a poor prognosis. In some cases these lymphomas are AIDSdefining. Epstein-Barr virus (EBV) or KSHV cause many of these lymphomas. Cervical cancer in HIV-infected women is considered AIDS-defining. It is caused by human papillomavirus (HPV). In addition to the AIDS-defining tumors listed above, HIV-infected patients are at increased risk of certain other tumors, such as Hodgkin's disease and anal and rectal carcinomas. However, the incidence of many common tumors, such as breast cancer or colon cancer, does not increase in HIV-infected patients. In areas where HAART is extensively used to treat AIDS, the incidence of many AIDS-related malignancies has decreased, but at the same time malignant cancers overall have become the most common cause of death of HIV-infected patients. AIDS patients often develop opportunistic infections that present with non-specific symptoms, especially low-grade fevers and weight loss. These include infection with Mycobacterium avium-intracellulare and cytomegalovirus (CMV). CMV can cause colitis, as described above, and CMV retinitis can cause blindness. Penicilliosis due to Penicillium marneffei is now the third most common opportunistic infection (after extrapulmonary tuberculosis and cryptococcosis) in HIV-positive individuals within the endemic area of Southeast Asia. The world Health Initiative on Dengue (WHIAIDS) will be launched in the 3rd quarter of 2010 along with WHIT and WHIL. WHIAIDS will be addressed along two categories: developing a Rapid Diagnosis Test Kit (RDT) and the treatment strategies (Drugs and Vaccine Development).

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Rapid Diagnosis: The diagnosis of AIDS in a person infected with HIV is based on the presence of certain signs or symptoms. Since June 5, 1981, many definitions have been developed for epidemiological surveillance such as the Bangui definition and the 1994 expanded World Health Organization AIDS case definition. However, clinical staging of patients was not an intended use for these systems as they are neither sensitive, nor specific. In developing countries, the World Health Organization staging system for HIV infection and disease, using clinical and laboratory data, is used and in developed countries, the Centers for Disease Control (CDC) Classification System is used. Many people are unaware that they are infected with HIV. Less than 1% of the sexually active urban population in Africa has been tested, and this proportion is even lower in rural populations. Furthermore, only 0.5% of pregnant women attending urban health facilities are counseled, tested or receive their test results. Again, this proportion is even lower in rural health facilities. Therefore, donor blood and blood products used in medicine and medical research are screened for HIV. HIV tests are usually performed on venous blood. Many laboratories use fourth generation screening tests which detect anti-HIV antibody (IgG and IgM) and the HIV p24 antigen. The detection of HIV antibody or antigen in a patient previously known to be negative is evidence of HIV infection. Individuals whose first specimen indicates evidence of HIV infection will have a repeat test on a second blood sample to confirm the results. The window period (the time between initial infection and the development of detectable antibodies against the infection) can vary since it can take 3–6 months to seroconvert and to test positive. Detection of the virus using polymerase chain reaction (PCR) during the window period is possible, and evidence suggests that an infection may often be detected earlier than when using a fourth generation EIA screening test. Positive results obtained by PCR are confirmed by antibody tests. Routinely used HIV tests for infection in neonates, born to HIV-positive mothers, have no value because of the presence of maternal antibody to HIV in the child's blood. HIV infection can only be diagnosed by PCR, testing for HIV pro-viral DNA in the children's lymphocytes Treatment Strategies: Current treatment for HIV infection consists of highly active antiretroviral therapy, or HAART. This has been highly beneficial to many HIV-infected individuals since its introduction in 1996 when the protease inhibitor-based HAART initially became available. Current optimal HAART options consist of combinations (or "cocktails") consisting of at least three drugs belonging to at least two types, or "classes," of antiretroviral agents. Typical regimens consist of two nucleoside analogue reverse transcriptase inhibitors (NARTIs or NRTIs) plus either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI). Because HIV disease progression in children is more rapid than in adults, and laboratory parameters are less predictive of risk for disease progression, particularly for young BRICKE INSTITUTE FOR GLOBAL HEALTH Page 43

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infants, treatment recommendations are more aggressive for children than for adults. In developed countries where HAART is available, doctors assess the viral load, rapidity in CD4 decline, and patient readiness while deciding when to recommend initiating treatment. Standard goals of HAART include improvement in the patient’s quality of life, reduction in complications, and reduction of HIV viremia below the limit of detection, but it does not cure the patient of HIV nor does it prevent the return, once treatment is stopped, of high blood levels of HIV, often HAART resistant. Moreover, it would take more than the lifetime of an individual to be cleared of HIV infection using HAART. Despite this, many HIV-infected individuals have experienced remarkable improvements in their general health and quality of life, which has led to the plummeting of HIV-associated morbidity and mortality. In the absence of HAART, progression from HIV infection to AIDS occurs at a median of between nine to ten years and the median survival time after developing AIDS is only 9.2 months. HAART is thought to increase survival time by between 4 and 12 years. For some patients, which can be more than fifty percent of patients, HAART achieves far less than optimal results, due to medication intolerance/side effects, prior ineffective antiretroviral therapy and infection with a drug-resistant strain of HIV. Non-adherence and non-persistence with therapy are the major reasons why some people do not benefit from HAART. The reasons for non-adherence and nonpersistence are varied. Major psychosocial issues include poor access to medical care, inadequate social supports, psychiatric disease and drug abuse. HAART regimens can also be complex and thus hard to follow, with large numbers of pills taken frequently. Side effects can also deter people from persisting with HAART, these include lipodystrophy, dyslipidaemia, diarrhoea, insulin resistance, an increase in cardiovascular risks and birth defects. Anti-retroviral drugs are expensive, and the majority of the world's infected individuals do not have access to medications and treatments for HIV and AIDS.

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ANNEX 3

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APPRECIATION

The following materials were consulted while this report was been prepared: Books, Magazines and Journals • Wellcome trust Dying for Change, Lab notes 5 published June 2004

• TDR’s Partnership for Malaria control: Engaging the formal and informal private sectors • TDR’s community directed interventions for major health problems in Africa: A multi-country study • TDR’s Use of Visceral leishmaniasis rapid Diagnostic Tests

• TDR’s Diagnostic Evaluation Series No 2: Laboratory based evaluation of 19 commercially available RDT for TB • TDR’s Neglected Diseases: Human Rights based approach to Neglected Tropical Diseases • TDR’s use of rapid Syphilis Test

• TDR’s Social Context of Schistosomiasis and its control: An introduction and annotated bibliography

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• to TB •

TDR’s report of the expert consultation on Immuno-therapeutic interventions

TDR’s diagnostics for Tuberculosis: Global demand and market potential pupal productivity survey

• TDR’s Multicountry study of Aedes aegypti methodology: findings and recommendations. • • • • TDR’s Eliminating River Blindness TDR’s scientific Working Group Report on TB TDR’s scientific Working Group Report on Dengue

TDR’s scientific Working Group Report on Schistosomiasis

Web Resources • • Wikipedia Center for Disease and Control (CDC)

ADMINISTRATIVE DETAILS

Bricke International is a biomedical research humanitarian charity established with the aim of reducing drastically mortality associated with poverty, infectious diseases, natural disasters, war and environmental upheavals. We understand that no government or organization can single handedly tackle a problem as vast as infectious disease in developing world, however, many different organizations including governments, charities and pharmaceutical companies could make a vital impact in particular areas and indeed a partnership of all these different organization might just be what we need to alleviate this situation. Public-Private Partnership (PPPs) is becoming a distinctive feature of the global healthcare landscape. One of the many advantages of PPPs is that they mobilize partners with different, even hostile philosophies around one common goal. PPPs make it possible to share risk and responsibility and they embody the principle of “win-win” solutions creating benefits for all parties. IDAAG has come to build a network of all these parties (governments, charities, pharmaceutical companies and NGOs in form of a Public-Private Partnership (PPPs) to finally stamp and alleviate the impact of Infectious Diseases in developing countries.

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Bricke International is registered with the Corporate Affairs Commission of Nigeria according to part 'C' of the Companies and Allied Matters Act, 1990 as a company with Echefu Multiventures as Trustee in 2006. Echefu Multiventures is a company limited by guarantee (registration number RC 118073) whose registered office is 8, Atanda Solanke Crescent, Olorunsogo, Abeokuta, Ogun State, Nigeria. The trustee is governed by its memorandum and articles of association. The directors (known as Governors) and the company secretary of the company are shown as follows: Board of Governors Echefu Bright (Chairman) Miss. Emeraghi Mary (Secretary) Mr. N.S Echefu B.Sc, M.Sc, MMP, PGDE Prof. C.F Mafiana B.Sc, M.Sc, PhD Prof. Titilola Akinremi (B.Sc, M.Sc, PhD, FRCP, FMedSci) Mr. Agoha Leo Udochukwu Bricke International is funded from a private endowment which is managed with long term stability and growth in mind. Its mission is to engage you in building a healthy world. Its work covers four areas: • Special Volunteer Schemes: Engaging in rural and community based volunteer projects that will ensure that the best health standards are brought to the doorstep of the masses. This will be achieved through our proposed Public Private Partnership. • Resources: Providing exceptional researchers in the area of disease management and vaccine research with the infrastructural and career support needed to fulfilling their potential. • Translation: Ensuring that maximum health benefits are gained from biomedical research • Advocacy: Raising awareness and educating people on the new and available approaches to the treatment of infectious diseases • Public Engagement: Engaging you in building a healthy world.

NETWORKING AND GOVERNANCE Bricke International is currently affiliated to as many organizations. It is also partnering with some of them on the implementation of most of its projects. Bricke International has a trustee, board of governors, associate fellows, Allies and patrons. An

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appointment to the board of governors is made by the incumbent governors after advertisement and wide consultation. The board of governors decides on strategic priorities, establishes funding policies and allocates budgets. The executive board chaired by a Chief Development Officer (CDO), report directly to the board of governors and he/she is responsible for the day to day management of Bricke International’s operations and activities.

COMMITTEES OF THE BOARD OF GOVERNORS The board of governors is assisted in its duties by a number of committees which report directly to it: Audit Committee: For matters of internal control, compliance with financial reporting requirements and relations with the external auditors. Remuneration committee: For remuneration issues Investment Committee: For matters relating to Bricke International investment Nomination Committee: For identifying potential candidates to fill board and committee vacancies and Academic Appraisal Committee: for matters relating to research strategy.

UNITS OF BRICKE INTERNATIONAL The following are the units of Bricke International. Each unit is headed by a Director. The coordinators of each of these units are members of Bricke International executive board. • Unit) • The Center for Global Health (Biomedical Research and Public Engagement

Bricke Humanitarian Services

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3.2

GLOSSARY

ACETAMINOPHEN: Drug used to prevent mouth blisters in measles cases ADENOVIRUSES: A group of DNA containing viruses found in man and animal species causing upper respiratory infections, pneumonia and epidemic keratoconjuctivitis. AIDS: An acronym for acquired Immune Deficiency Syndrome. An Infection caused by the HIV BRICKE INSTITUTE FOR GLOBAL HEALTH Page 51

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ALZHEIMER’S DISEASE: A dementing disease which is most commonly referred to as pre-senile dementia. It’s a specific brain abnormality. ANTIMALARIAL: Drugs that can be used against malaria ANTIBIOTICS: Antibacterial substances derived from fungi and bacteria. Exemplified by penicillin. ASYMPTOMATIC: A situation where a disease hasn’t shown any symptom to suggest that one has been infected with it ATOPIC SYNDROME: A constitutional tendency to develop infantile eczema, asthma, hay fever or all three when there is a positive family history. ATAXIA TELANGIECTASIA: This is a differential diagnosis resulting from T-cell deficiency and characterized by telangiectasis, ataxia, and recurrent Sino-pulmonary infection in HIV/AIDS cases BACTERIA: Group of micro organisms that causes disease conditions BCG: Bacille Calmette-Guérin: A vaccine for TB treatment BILHARZIA: Another name for Schistosomiasis CAMPYLOBACTER INFECTION: Gram negative motile rod bacterium. It causes an acute diarrhoeal illness lasting several days. CANCER: General term used to describe any malignant growth in any part of the body CARDIOVASCULAR DISEASES: Diseases that affect the heart and the blood vessels CHAGAS' DISEASE: A disease caused by Trypanosoma cruzi and transmitted by "Kissing" (triatomine) bugs COUNTERFEIT DRUGS: Another name for fake and substandard drugs CENTRAL NERVOUS SYSTEM: The system of the body that coordinates all reflex and non reflex actions. That is the system in which the brain and the spinal cord fall. CELSIUS: A unit for measuring temperature CONTAGIOUS: Something that is capable of transmitting an infection CIRRHOSIS OF THE LIVER: Hardening of the liver CYTOMEGALOVIRUS: Belongs to the same group of viruses with herpes simplex CONGENITAL INFECTIONS: Abnormal conditions present at birth. Most times they are hereditary. BRICKE INSTITUTE FOR GLOBAL HEALTH Page 52

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CROUP: Laryngeal obstruction COXSACKIE VIRUSES: A virus belonging to the family Enteroviruses. It causes aseptic meningitis DEVELOPING COUNTRIES: Countries with very low GDP (Gross domestic product) DISEASES: A deviation from or an interruption to the normal functioning of any part if the body DISPENSARY: A place in the hospital or school where drugs are stored for treatment purposes DRUGS: The generic name for any substance used for the prevention, diagnosis and treatment of diagnosed diseases and also to relief symptoms DIABETES: A disease condition arising from low insulin level hence a high blood sugar level. It is characterized by polyuria. DOTS: Directly Observed therapy Short Course. A strategy employed in the treatment of TB and some highly contagious infections DIARRHEA: A deviation from established bowel rhythm characterized by an increase in frequency and fluidity of the stools ESCHERICHIA COLI: A bacterium that causes enteritis EPISTAXIS: Nose bleeding EPSTEIN BARR VIRUS: A virus that causes mononucleosis ELISA: Enzyme Linked Immunosorbent Assay ELEPHANTIASIS: another name for Lymphatic filariasis ENTEROVIRUSES: viruses that typically cause stomach "flu FDA: Food and Drug Administration FAHRENHEIT: another unit used in the expression of temperature FONTANELLES: Fontanelles are the soft spot at the top/front of the baby's skull, where the bones of the skull join

GENETIC ENGINEEERING: A biomedical application of genes GERMS: Unicellular microorganism that are pathogenic BRICKE INSTITUTE FOR GLOBAL HEALTH Page 53

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GASTROINTESTINAL INFECTIONS: Infections that affect the stomach and the intestine GONORRHEA: Sexually transmitted disease in adults HEPATITIS: An inflammation of the liver HBV: Hepatitis B virus. HEPATITIS A: Infectious Hepatitis HANSEN'S DISEASE: Another name for leprosy HAART: Highly Active Antiretroviral Therapy HAEMOPHILUS INFLUENZAE TYPE B (HIB): The leading cause of meningitis in children in the United States HIV: (Human Immunodeficiency virus) the causative agent for AIDS INFECTIOUS DISEASES: A disease caused by a specific, pathogenic, organism and capable of being transmitted to another individual by direct contact INFLUENZA: An acute viral infection of the nasopharynx and respiratory tract which occurs in epidemic or pandemic form. INFLAMMATION: The reaction of living tissues to injury, infection or irritation, characterized by pain, swelling, redness and heat. LEPROSY: Progressive or contagious disease, endemic in warmer climates and characterized by granulomatous formation in the nerves or on the skin. It is caused by a bacteria, mycobacterium leprae LYMPHATIC FILARIASIS: Another name for elephantiasis LUMBAR PUNCTURE: The withdrawal of the cerebrospinal fluid through a hollow needle inserted into the subarachnoid space in the lumbar region LYMPHOCYTIC CHORIOMENINGITIS (LCM): Disease transmitted by rodents, gerbils and fishes MENINGES: The surrounding membrane of the brain and the spinal cord MICROORGANISM: Disease causing organisms MALARIA: A disease condition caused by a plasmodium parasite MALAISE: feeling of illness or discomfort MYCOBACTERIA MARINUM: This infection may occur in people exposed to contaminated water in aquariums or pools.

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MDG: Millennium Development Goals MMR : Measles, Mumps and Rubella (MMR) vaccine MUMPS: An acute, specific inflammation of the parotid glands caused by a virus MEASLES: An acute viral infectious disease MALNUTRITION: The state of being poorly nourished MICROBIOLOGY: A field of biological sciences that deals with the study of micro organisms NGO: Non Governmental Agencies NEUROLOGICAL: That has to do with the nervous system NEISSERIA MENINGITIDIS: The bacteria that caused bacterial meningitis NAUSEA: feeling of impending vomiting OSTEOMYELITIS: Inflammation commencing in the bone marrow PARAMEDICS: Associated with the medical profession PATHOLOGY: The study of the cause and nature of diseases PARALYSIS: Complete or an incomplete loss of nervous function to a part of the body PLAGUE: Very contagious epidemic disease pseudotuberculosissyn petis and spread by rats PERTUSSIS: Otherwise called whooping cough PPP: Public Private Partnership ROTAVIRUS: Viruses associated with gastroenteritis in children RETROVIRALS: RNA viruses in which the HIV belongs to SEPSIS: A process of being infected with a pus-producing organism STDS: Sexually Transmitted Diseases SARS: Severe Acute Respiratory syndrome SCHISTOSOMIASIS: A trypanosome infection TB: Tuberculosis UNICEF: United Nations Children Fund caused by Yersinia

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UNFPA: United Nations Agency Food and population Agency VIRUS: Very small microorganism which is parasitic in living cells VACCINE: Suspension or products of infectious agents used chiefly for producing active immunity WHO: The World Health Organization

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BRICKE INSTITUTE FOR GLOBAL HEALTH

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[INFECTIOUS DISEASES IN WEST AFRICA] CASE STUDY

BRICKE INSTITUTE FOR GLOBAL HEALTH

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