Many terrifying diseases have long afflicted humans in the warm, wet places of the world. Evidence of some of them is found in mummified Egyptians; others are recorded in the Bible and the Talmud, and the writings of ancient scholars such as Hippocrates. Modern science has established that they are transmitted by parasitic worms, bacteria, viruses, protozoans and fungi.
Some have names that may be unfamiliar. Buruli ulcer, Chagas disease, guinea-worm disease, leishmaniasis, river blindness, trachoma and yaws are some of the 18 now collectively referred to as “neglected tropical diseases” (NTDs). Between them they affect more than a billion people, most of them poor, with blindness, immobility, disfigurement and often great pain. The resulting disabilities keep sufferers mired in poverty; that poverty is also what allows the diseases to thrive.
Medicine is now capable of cutting transmission and driving many NTDs out of existence by 2030. Simple remedies that were already available. In the 1950s and 1960s, China eliminated lymphatic filariasis by adding an anti-parasitic drug to table salt. For sleeping sickness, surveillance and “vector control” (such as spraying with insecticide and setting insect traps) were highly effective. Insecticides were also known to work against other diseases. One of the reasons Japan and South Korea developed so fast after the second world war is that both ran major deworming programmes in schools.
The drug ivermectin was developed by Merck in the 1970s for parasitic infections in animals. The first human trial of ivermectin for river blindness was in Senegal in 1981, in patients who had the early stages of the disease but no damage to their eyes. Together with several more trials, it showed that ivermectin was safe in humans and highly effective at killing the disease vector in its larval state.
But Merck had a problem: there was no market for it. Those who needed ivermectin were too poor to buy it. So the firm did something remarkable: it made an open-ended commitment to give away as much of the drug as necessary, starting in 1987, with the ultimate goal of eliminating river blindness entirely. In the following decade it donated 100m doses.
Yet a miracle cure was not enough. The biggest obstacle to tackling river blindness, and other NTDs, turned out to be getting the drug to those who needed it. That was too complicated for any one company on its own. Painstaking and costly logistical efforts were required to get treatments to remote areas. Prevalences had to be mapped, and, for some of the diseases, individual patients diagnosed. Since most of the affected areas lacked health-care workers, some had to be trained. The stigma and disability faced by sufferers meant that many were hidden within their communities; they had to be found and persuaded to accept treatment. And after all that, surveillance and follow-ups were required to stop diseases making a comeback.
Partnerships started to emerge between countries where NTDs were endemic. International institutions such as the World Bank and World Health Organisation (WHO) teamed up with donor governments and charities. By 1999 the Gates Foundation, a charity set up by Bill and Melinda Gates, was funding work in lymphatic filariasis and schistosomiasis, a debilitating ailment caused by a parasitic worm transmitted by freshwater snails.
By then the long-running effort to eradicate guinea worm led by the Carter Centre, a foundation set up by Jimmy Carter in 1982, had gained pace. The worm’s larvae are ingested in dirty water and grow internally to as long as a metre; they emerge, agonisingly, through the skin over several weeks. The only treatment for an established case, even now, is to speed up this expulsion by gradually winding the worm’s emerging body on a stick. But public-information campaigns about the need to filter drinking water and keep sufferers away from water sources, where they might pass on the infection, have brought new cases down from an estimated 3.5m a year globally in 1986, when eradication efforts started, to 25 last year.
Other drug firms, including GSK, Pfizer and Novartis, started to donate medicines on a large scale for other conditions. These included albendazole, another anti-parasitic for lymphatic filariasis; azithromycin, an antibiotic that works against trachoma (a bacterial infection that can cause blindness); and a combination of drugs for leprosy (another bacterial infection, which leads to skin lesions and nerve damage). Yet these disjointed initiatives added up to less than what was needed. In an article in 2004 in the Lancet, a medical journal, Dr Molyneux argued that these diseases were unfairly neglected in comparison with tuberculosis, malaria and HIV/AIDS, which were the subject of well-funded global programmes. Experience in a range of countries showed that these diseases could be controlled, he reminded his readers—and doing so brought dividends besides the relief of great suffering.
For example, the control of river blindness in west Africa has been described by the World Bank as one of the most cost-effective ways to reduce premature death and disability in poor countries. Each dollar spent on the control of lymphatic filariasis in China, or Chagas disease in Brazil, has been estimated to produce benefits of $15 and $17 respectively, by reducing spending on treatment and cutting the number of prematurely curtailed working lives. Some disease-control programmes had built logistics for distributing drugs from scratch, which could be used for other public-health efforts, and had strengthened national health systems more broadly.
By the turn of the millennium the common features of a group of tropical diseases were increasingly recognised by public-health experts, donors and the WHO. They were diseases of poverty but also causes of poverty. They caused disability and made it harder to absorb nutrients in food; reduced school attendance, thus condemning children to a life of grunt work; and trapped families in poverty when breadwinners were too sick to work or farm. Though prevention and treatment methods varied, there was clear potential for combining attempts to control or even eradicate them. Some required the suppression of vectors such as flies and mosquitoes, for example by spraying insecticides or distributing bednets. Some could be tackled by dosing entire communities with cheap, safe drugs; others by identifying and managing individual cases over extended periods. And most could be greatly reduced by providing safe drinking water, sanitation and information about hygiene.
The Gates Foundation has helped a lot. In 2010 Mr Gates and Tachi Yamada, who led the foundation’s global health programme at the time, invited the bosses of a group of drug companies to tell them what could be done to tackle the field’s greatest challenges. The firms said that they wanted help to deliver the free drugs that they were offering. At around the same time the WHO created a detailed plan for controlling each of the NTDs.
Finally, the stage was set for an ambitious global coalition. Margaret Chan, the director-general of the WHO, and Mr Gates were able to rally charities, NGOs, big donors (such as the governments of America, Britain and the United Arab Emirates) and, crucially, 13 drug firms. Many, including Merck KGaA, Johnson & Johnson and Gilead, had been donating treatments for years. Others, including Eisai, a Japanese firm, were new to the fight. Together, they declared themselves ready to give away drugs worth billions of dollars each year. In 2012 the group signed the “London Declaration” which promised to control, eliminate or eradicate ten NTDs by the end of the decade.
Five would be controlled with mass drug administration: lymphatic filariasis, river blindness, schistosomiasis, trachoma and diseases caused by helminths (parasitic worms such as hookworm and roundworm) that spend part of their lifecycles in soil. Tackling the rest, including sleeping sickness and Chagas disease—both parasitic diseases transmitted by insect bites—would require the identification and treatment of infected individuals.
Since the signing of the London declaration, the alliance against NTDs has developed into the largest and most successful public-health initiative in history. The number of people at risk globally from NTDs has fallen by 20%. Most of Latin America has eliminated river blindness. The number of new cases of leprosy has declined in eight of the past nine years. In the past year eight countries eliminated lymphatic filariasis. The number of cases of sleeping sickness is at its lowest in 75 years, and eradication is now thought possible. In 2015, 1.5bn treatment doses were donated by drug firms, and almost a billion people received them—an increase of more than a third since 2012.
Critics of foreign aid often charge that it weakens the countries that receive it, by undermining their economies and governance. But support for tackling NTDs, and other health problems, has shown quite the opposite effect. It removes an obstacle that stops abjectly poor people bettering themselves. And, like efforts to control malaria, tuberculosis and HIV/AIDS, it improves public-health systems and disease surveillance. As countries become more organised they can often combine their programmes. The excellent results are persuading some recipient countries to chip in: a quarter of programmes on NTDs in the Democratic Republic of Congo, for example, are now locally funded, up from none in 2011. Aid given to set up the infrastructure needed to tackle polio in Nigeria meant that the country was better placed to fight Ebola when that disease emerged.
To elimination and beyond
It is tempting to extrapolate, and predict that all 18 NTDs will be consigned to history. Progress might even speed up: new diagnostic tools and treatments are on their way. The Gates Foundation is paying for final trials of a triple-drug therapy for lymphatic filariasis that clears the parasite from infected people’s bodies far more effectively than current treatments. When they are completed later this year, India might be able to get rid of the disease in just a couple of years, and other countries could quickly follow.
Mr Gates thinks that it should also be possible to get visceral leishmaniasis, a parasitic disease that destroys the internal organs, down to tiny numbers of new infections in Asia. (To public-health aficionados, “eliminating” a disease means making it rare, rather than completely eradicating it.) By 2030 he hopes to see just 170m people globally at risk of NTDs, down from 1.7bn now. For that to happen drug companies will need to remain strongly committed; that means making sure they receive “well-deserved” credit, he says.
But what worries some, including the authors of the WHO’s latest report on NTDs, published on April 19th at a summit in Geneva to evaluate progress and gather new donations, is the endgame. “Sometimes the last mile is the hardest,” says Ken Gustavsen, who runs corporate responsibility for Merck. As efforts to control a disease are successful, the sense of urgency fades, making it hard to maintain the political momentum. Tackling some of the NTDs requires long-term commitment. Chagas will have to be tracked into the remote reaches of the Amazon basin; diminished concern about canine rabies is already weakening attempts to eradicate it in Latin America. A campaign in 1952-64 against yaws, a bacterial infection that attacks skin, bone and cartilage, provides an object lesson. As cases became fewer, funding and attention shifted away, and in the 1970s the disease rebounded.
There are fears that something similar could happen with guinea-worm disease. Its imminent demise has been declared prematurely several times in recent years. Last year’s tally of 25 reported cases was slightly higher than the figure for 2015. Fortunately, it can be transmitted only if an infected person enters drinking water around the time when a worm is leaving the body, meaning the disease would be slow to bounce back, unlike, say, polio, which is passed on through fecal matter and could quickly return from near-extinction if eradication efforts were to slacken.
But wiping out guinea-worm disease, as the London declaration envisages, and controlling or eliminating the other NTDs, will take continued focus—and plenty more money. A big worry is whether the governments that fund much drug distribution, chief among them America’s and Britain’s, will continue to do so. This week the British government said it would double spending on NTDs over the next five years, to £360m ($460m). But the department responsible for aid was reluctant to provide a spokesman to discuss the programme. And a turn to insularity in many rich countries means foreign aid is increasingly criticised. British newspapers have become strikingly hostile towards it, arguing that most is squandered, and that even if it were not, the money is needed to cut poverty at home. The Daily Mail, one of the most splenetic, frequently splashes stories of wasted aid on its front page (often blaming the European Union). It is campaigning for Britain’s government to abandon a pledge, passed into law in 2015, to earmark 0.7% of GDP for foreign aid.
In America Donald Trump’s administration has said it wants to slash the budget of the state department, the part of government responsible for most foreign-aid spending. Mr Gates, who recently met Mr Trump, remarks that it is unlikely Congress will allow drastic cuts. But even a modest trimming of American spending on NTDs would be worrisome, if it discouraged spending by other governments.
Private donors could fill part of the gap, but not all. Plenty find the cause appealing, says Ellen Agler of the END Fund, which co-ordinates philanthropy for NTDs with those of governments and international organisations: “The clear return on investment is so powerful, and the timeline is so short.” Since the fund was set up in 2012 it has treated more than 140m people at risk in 26 countries, and raised more than $75m from individuals, corporate foundations and philanthropic groups. Its donors bring more than their money, says Ms Agler: they strengthen oversight, and provide private-sector problem-solving skills—and sometimes local contacts and logistical support.
The effort to defeat NTDs produces plenty of heart-warming stories. In Tanzania Ms Mwingira talks about men with lymphatic filariasis who have received surgery to reduce the size of their genitals and can return to normal life, marry and have children. Kofi Nyarko, a former leprosy patient who lives in Ghana, says he would be dead without treatment. It came too late to save his hands from deformity; they are twisted and rigid. But he has been able to achieve his dream of becoming a special-needs teacher.
Where charity begins
It is worth recalling the motivation for Merck’s original decision, back in 1987, to donate ivermectin for river blindness, says Mr Gustavsen. There was no economic rationale: the firm’s scientists simply felt it was the right thing to do. Having discovered the drug, and established that it worked against a disease that caused awful suffering, neglecting to use it would have been “incredibly demoralising”, he says. That sense of moral purpose must not weaken if the global coalition against NTDs is finally to prevail.
LYMPHATIC FILARIASIS elephantiasis tropica, elephantiasis arabum
Lymphatic filariasis, also known as elephantiasis, is a human disease caused by parasitic worms known as filarial worms. Most cases of the disease have no symptoms. Some people, however, develop a syndrome called elephantiasis, which is marked by severe swelling in the arms, legs, or genitals. The skin may become thicker as well, and the condition may become painful. The changes to the body may harm the affected person’s social and economic situation
The worms are spread by the bites of infected mosquitoes. Three types of worms are known to cause the disease: Wuchereria bancrofti, Brugia malayi, and Brugia timori, with Wuchereria bancrofti being the most common. These worms damage the lymphatic system. The disease is diagnosed by microscopic examination of blood collected during the night. The blood is typically examined as a smear after being stained with Giemsa stain. Testing the blood for antibodies against the disease may also permit diagnosis. Other roundworms from the same family are responsible for river blindness.
Prevention can be achieved by treating entire groups in which the disease exists, known as mass deworming. This is done every year for about six years, in an effort to rid a population of the disease entirely. Medications used include antiparasitics such as albendazole with ivermectin, or albendazole with diethylcarbamazine. The medications do not kill the adult worms but prevent further spread of the disease until the worms die on their own. Efforts to prevent mosquito bites are also recommended, including reducing the number of mosquitoes and promoting the use of bed nets.
In 2015 about 38.5 million people were infected. About 950 million people are at risk of the disease in 54 countries. It is most common in tropical Africa and Asia. Lymphatic filariasis is classified as a neglected tropical diseases and one of the four main worm infections. The disease results in economic losses of many billions of dollars a year.
Signs and symptoms. The most spectacular symptom of lymphatic filariasis is elephantiasis, a stage 3 lymphedema with thickening of the skin and underlying tissues. This was the first mosquito-borne disease to be discovered. Elephantiasis results when the parasites lodge in the lymphatic system and cause blockages to the flow of lymph. Infections usually begin in childhood. The skin condition the disease causes is called “elephantiasis tropica” (also known as “elephantiasis arabum”).
Elephantiasis mainly affects the lower extremities; the ears, mucous membranes, and amputation stumps are affected less frequently. However, various species of filarial worms tend to affect different parts of the body: Wuchereria bancrofti can affect the arms, breasts, legs, scrotum, and vulva (causing hydrocele formation), while Brugia timori rarely affects the genitals. Those who develop the chronic stages of elephantiasis are usually amicrofilaraemic and often have adverse immunological reactions to the microfilariae as well as the adult worms. Elephantiasis leads to marked swelling of the lower half of the body.
The subcutaneous worms present with skin rashes, urticarial papules, and arthritis, as well as hyper- and hypopigmentation macules. Serous cavity filariasis presents with symptoms similar to subcutaneous filariasis, in addition to abdominal pain, because these worms are also deep-tissue dwellers.
Life cycle of Wuchereria bancrofti. Elephantiasis occurs in the presence of microscopic, thread-like parasitic worms such as Wuchereria bancrofti (the most common), Brugia malayi, and Brugia timori (also known as B. timori), all of which are transmitted by bites from infected mosquitoes. It is a type of helminth infection. Three types of worm cause the disease and damage the lymphatic system:
The disease itself is a result of a complex interplay between several factors: the worm, the endosymbiotic Wolbachia bacteria within the worm, the host’s immune response, and the numerous opportunistic infections and disorders that arise. The adult worms only live in the human lymphatic system. The parasite infects the lymph nodes and blocks the flow of lymph throughout the body; this results in chronic lymphedema, most often noted in the lower torso (typically in the legs and genitals).
Diagnosis. The standard method for diagnosing active infection is by finding the microfilariae via microscopic examination. This may be difficult, as in most parts of the world, microfilariae only circulate in the blood at night. For this reason, the blood has to be collected nocturnally. The blood sample is typically in the form of a thick smear and stained with Giemsa stain. Testing the blood serum for antibodies against the disease may also be used.
Prevention. The World Health Organization recommends mass deworming—treating entire groups of people who are at risk with a single annual dose of two medicines, namely albendazole in combination with either ivermectin or diethylcarbamazine citrate.With consistent treatment, since the disease needs a human host, the reduction of microfilariae means the disease will not be transmitted, the adult worms will die out, and the cycle will be broken. In sub-Saharan Africa, albendazole (donated by GlaxoSmithKline) is being used with ivermectin (donated by Merck & Co.) to treat the disease, whereas elsewhere in the world, albendazole is used with diethylcarbamazine. Transmission of the infection can be broken when a single dose of these combined oral medicines is consistently maintained annually for a duration of four to six years. Using a combination of treatments better reduces the number of microfilariae in blood. Avoiding mosquito bites, such as by using insecticide-treated mosquito bed nets, also reduces the transmission of lymphatic filariasis.
The Carter Center’s International Task Force for Disease Eradication declared lymphatic filariaisis one of six potentially eradicable diseases.[17] According to medical experts, the worldwide effort to eliminate lymphatic filariasis is on track to potentially succeed by 2020.
For similar-looking but causally unrelated podoconiosis, international awareness of the disease will have to increase before elimination is possible. In 2011, podoconiosis was added to the World Health Organization’s Neglected Tropical Diseases list, which was an important milestone in raising global awareness of the condition. The efforts of the Global Programme to Eliminate LF are estimated to have prevented 6.6 million new filariasis cases from developing in children between 2000 and 2007, and to have stopped the progression of the disease in another 9.5 million people who had already contracted it.
Treatment. Treatments for lymphatic filariasis differ depending on the geographic location of the endemic area. In sub-Saharan Africa, albendazole is being used with ivermectin to treat the disease, whereas elsewhere in the world, albendazole is used with diethylcarbamazine. Geo-targeting treatments is part of a larger strategy to eventually eliminate lymphatic filariasis by 2020.
Additionally, surgical treatment may be helpful for issues related to scrotal elephantiasis and hydrocele. However, surgery is generally ineffective at correcting elephantiasis of the limbs.[citation needed] A vaccine is not yet available.
Treatment for podoconiosis consists of consistent shoe-wearing (to avoid contact with the irritant soil) and hygiene – daily soaking in water with an antiseptic (such as bleach) added, washing the feet and legs with soap and water, application of ointment, and in some cases, wearing elastic bandages. Antibiotics are used in cases of infection.
Antibiotics. The antibiotic doxycycline is effective in treating lymphatic filariasis. Its drawbacks are that it requires a 4 to 6 weeks treatment and should not be used in young children and pregnant women, which limits its use for mass prevention.[27] The parasites responsible for elephantiasis have a population of endosymbiotic bacteria, Wolbachia, that live inside the worm. When the symbiotic bacteria of the adult worms are killed by the antibiotic, they no longer provide chemicals which the nematode larvae need to develop, which either kill the larvae or prevent their normal development. This permanently sterilizes the adult worms, which additionally die within 1 to 2 years instead of 10 to 14 years lifespan.
Prognosis. About 40 million people were disfigured or incapacitated by the disease in 2015. Elephantiasis caused by lymphatic filariasis is one of the most common causes of disability in the world. In endemic communities, approximately 10 percent of women can be affected with swollen limbs, and 50 percent of men can have mutilating genital disease. In areas endemic for podoconiosis, prevalence can be 5% or higher.
Epidemiology. A 2012 report noted that lymphatic filariasis affected 120 million people[31] and one billion people at risk for infection. It is considered endemic in tropical and subtropical regions of Africa, Asia, Central and South America, and Pacific Island nations. Filariasis is considered endemic in 73 countries; 37 of these are in Africa.
In the Americas, it is present in Brazil, Costa Rica, the Dominican Republic, Guyana, Haiti, Suriname, and Trinidad and Tobago.
In Asia, it is present in Bangladesh, Cambodia, India, Indonesia, Laos, Malaysia, Maldives, the Philippines, Sri Lanka, Thailand, Timor-Leste, and Vietnam. In the Middle East, it is present only in Yemen. In the Pacific region, it is endemic in American Samoa, the Cook Islands, Fiji, French Polynesia, Micronesia, Niue, Papua New Guinea, Samoa, Tonga, Tuvalu, and Vanuatu.
In many of these countries, considerable progress has been made towards elimination of filariasis. Elimination of the disease may have been achieved in several countries, but awaits official confirmation by the WHO.
RIVER BLINDNESS Onchocerciasis
Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm Onchocerca volvulus. Symptoms include severe itching, bumps under the skin, and blindness. It is the second most common cause of blindness due to infection, after trachoma.
The parasite worm is spread by the bites of a black fly of the Simulium type. Usually, many bites are required before infection occurs. These flies live near rivers, hence the name of the disease. Once inside a person, the worms create larvae that make their way out to the skin. Here, they can infect the next black fly that bites the person. There are a number of ways to make the diagnosis including: placing a biopsy of the skin in normal saline and watching for the larva to come out, looking in the eye for larvae, and looking within the bumps under the skin for adult worms.
A vaccine against the disease does not exist. Prevention is by avoiding being bitten by flies. This may include the use of insect repellent and proper clothing. Other efforts include those to decrease the fly population by spraying insecticides. Efforts to eradicate the disease by treating entire groups of people twice a year is ongoing in a number of areas of the world. Treatment of those infected is with the medication ivermectin every six to twelve months. This treatment kills the larva but not the adult worms. The antibiotic doxycycline weakens the worms by killing an associated bacterium called Wolbachia, and is recommended by some as well. The lumps under the skin may also be removed by surgery.
About 15.5 million people are infected with river blindness. Approximately 0.8 million having some amount of loss of vision from the infection. Most infections occur in sub-Saharan Africa, although cases have also been reported in Yemen and isolated areas of Central and South America. It is listed by the World Health Organization as a neglected tropical disease.[10]
Signs and symptoms. Adult worms remain in subcutaneous nodules, limiting access to the host’s immune system. Microfilariae, in contrast, are able to induce intense inflammatory responses, especially upon their death. 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. Dying microfilariae have been recently discovered to release Wolbachia surface protein that activates TLR2 and TLR4, triggering innate immune responses and producing the inflammation and its associated morbidity. The severity of illness is directly proportional to the number of infected microfilariae and the power of the resultant inflammatory response.
Skin involvement typically consists of intense itching, swelling, and inflammation: Acute papular onchodermatitis – scattered pruritic papules. Chronic papular onchodermatitis – larger papules, resulting in hyperpigmentation. Lichenified onchodermatitis – hyperpigmented papules and plaques, with edema, lymphadenopathy, pruritus and common secondary bacterial infections. Skin atrophy – loss of elasticity, the skin resembles tissue paper, ‘lizard skin’ appearance. Depigmentation – ‘leopard skin’ appearance, usually on anterior lower leg.
Glaucoma effect – eyes malfunction, begin to see shadows or nothing. Ocular involvement provides the common name associated with onchocerciasis, river blindness, and may involve any part of the eye from conjunctiva and cornea to uvea and posterior segment, including the retina and optic nerve. 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. Some evidence suggests the effect on the cornea is caused by an immune response to bacteria present in the worms.
Nodding disease. This is an unusual form of epidemic epilepsy associated with onchocerciasis.
Life cycle. The life of the parasite can be traced through the black fly and the human hosts in the following steps: A Simulium female black fly takes a blood meal on an infected human host, and ingests microfilaria. The microfilaria enter the gut and thoracic flight muscles of the black fly, progressing into the first larval stage. The larvae mature into the second larval stage, and move to the proboscis and into the saliva in its third larval stage. Maturation takes about seven days. The black fly takes another blood meal, passing the larvae into the next human host’s blood. The larvae migrate to the subcutaneous tissue and undergo two more molts. They form nodules as they mature into adult worms over six to 12 months.
After maturing, adult male worms mate with female worms in the subcutaneous tissue to produce between 700 and 1,500 microfilaria per day. The microfilaria migrate to the skin during the day, and the black flies only feed in the day, so the parasite is in a prime position for the female fly to ingest it. Black flies take blood meals to ingest these microfilaria to restart the cycle.
Prevention. Various control programs aim to stop onchocerciasis from being a public health problem. The first was the Onchocerciasis Control Programme (OCP), which was launched in 1974, and at its peak, covered 30 million people in 11 countries. Through the use of larvicide spraying of fast-flowing rivers to control black fly populations, and from 1988 onwards, the use of ivermectin to treat infected people, the OCP eliminated onchocerciasis as a public health problem.
No vaccine to prevent onchocerciasis infection in humans is available.
Treatment. In mass drug administration (MDA) programmes, the treatment for onchocerciasis is ivermectin (trade name: Mectizan); infected people can be treated with two doses of ivermectin, six months apart, repeated every three years. The drug paralyses and kills the microfilariae causing fever, itching, and possibly oedema, arthritis and lymphadenopathy. Intense skin itching is eventually relieved, and the progression towards blindness is halted. In addition, while the drug does not kill the adult worms, it does prevent them for a limited time from producing additional offspring. The drug therefore prevents both morbidity and transmission for up to several months. Ivermectin treatment is particularly effective because it only needs to be taken once or twice a year, needs no refrigeration, and has a wide margin of safety, with the result that it has been widely given by minimally trained community health workers.[28]
Antibiotics. For the treatment of individuals, doxycycline is used to kill the Wolbachia bacteria that live in adult worms. This adjunct therapy has been shown to significantly lower microfilarial loads in the host, and may kill the adult worms, due to the symbiotic relationship between Wolbachia and the worm.
Epidemiology. About 37 million people are infected with this parasite; about 300,000 of those had been permanently blinded.[38] As of 2008, about 99% of onchocerciasis cases occurred in Africa. Onchocerciasis is currently endemic in 30 African countries, Yemen, and isolated regions of South America. Over 85 million people live in endemic areas, and half of these reside in Nigeria. Another 120 million people are at risk for contracting the disease. Due to the vector’s breeding habitat, the disease is more severe along the major rivers in the northern and central areas of the continent, and severity declines in villages farther from rivers.[citation needed] Onchocerciasis was eliminated in the northern focus in Chiapas, Mexico, and the focus in Oaxaca, Mexico, where Onchocerca volvulus existed, was determined, after several years of treatment with ivermectin, as free of the transmission of the parasite.
According to a 2002 WHO report, onchocerciasis has not caused a single death, but its global burden is 987,000 disability adjusted life years (DALYs). The severe pruritus alone accounts for 60% of the DALYs. Infection reduces the host’s immunity and resistance to other diseases, which results in an estimated reduction in life expectancy of 13 years.[40]
History. Onchocerca originated in Africa and was exported to the Americas by the slave trade,
GUINEA WORM Dracunculiasis
Dracunculiasis, also called Guinea-worm disease (GWD), is an infection by the Guinea worm. A person becomes infected when they drink water that contains water fleas infected with guinea worm larvae. Initially there are no symptoms. About one year later, the person develops a painful burning feeling as the female worm forms a blister in the skin, usually on a lower limb. The worm then emerges from the skin over the course of a few weeks. During this time, it may be difficult to walk or work. It is very uncommon for the disease to cause death.
In humans, the only known cause is Dracunculus medinensis. The worm is about one to two millimeters wide, and an adult female is 60 to 100 centimeters long (males are much shorter at 12–29 mm or 0.47–1.14 in). Outside of humans, the young form can survive up to three weeks, during which they must be eaten by water fleas to continue to develop. The larva inside water fleas may survive up to four months. Thus, in order for the disease to remain in an area, it must occur each year in humans. A diagnosis of the disease can usually be made based on the signs and symptoms.
Prevention is by early diagnosis of the disease followed by keeping the person from putting the wound in drinking water to decrease spread of the parasite. Other efforts include improving access to clean water and otherwise filtering water if it is not clean. Filtering through a cloth is often enough. Contaminated drinking water may be treated with a chemical called temefos to kill the larva. There is no medication or vaccine against the disease. The worm may be slowly removed over a few weeks by rolling it over a stick. The ulcers formed by the emerging worm may get infected by bacteria. Pain may continue for months after the worm has been removed.
In 2015 there were 22 reported cases of the disease while in 2016 there were 25. This is down from an estimated 3.5 million cases in 1986. In 2016 the disease occurred in three countries, all in Africa, down from 20 countries in the 1980s. It will likely be the first parasitic disease to be globally eradicated.
Guinea worm disease has been known since ancient times. It is mentioned in the Egyptian medical Ebers Papyrus, dating from 1550 BC. The name dracunculiasis is derived from the Latin “affliction with little dragons”, while the name “guinea worm” appeared after Europeans saw the disease on the Guinea coast of West Africa in the 17th century. Other Dracunculus species are known to infect various mammals, but do not appear to infect humans. Dracunculiasis is classified as a neglected tropical disease. Because dogs may also become infected, the eradication program is monitoring and treating dogs as well.
Signs and symptoms. Dracunculiasis is diagnosed by seeing the worms emerging from the lesions on the legs of infected individuals and by microscopic examinations of the larvae. As the worm moves downwards, usually to the lower leg, through the subcutaneous tissues, it leads to intense pain localized to its path of travel. The burning sensation experienced by infected people has led to the disease being called “the fiery serpent”. Other symptoms include fever, nausea, and vomiting. Female worms cause allergic reactions during blister formation as they migrate to the skin, causing an intense burning pain. Such allergic reactions produce rashes, nausea, diarrhea, dizziness, and localized edema. When the blister bursts, allergic reactions subside, but skin ulcers form, through which the worm can protrude. Only when the worm is removed is healing complete. Death of adult worms in joints can lead to arthritis and paralysis in the spinal cord.
Life cycle of Dracunculus medinensis. Dracunculiasis is caused by drinking water contaminated by water fleas that host the D. medinensis larvae. Dracunculiasis has a history of being very common in some of the world’s poorest areas, particularly those with limited or no access to clean water. In these areas, stagnant water sources may still host copepods, which can carry the larvae of the guinea worm.
After ingestion, the copepods die and are digested, thus releasing the stage 3 larvae, which then penetrate the host’s stomach or intestinal wall, and then enter into the abdominal cavity and retroperitoneal space. After maturation, which takes approximately three months, mating takes place; the male worm dies after mating and is absorbed by the host’s body.
Approximately one year after mating, the fertilized females migrate in the subcutaneous tissues adjacent to long bones or joints of the extremities. They then move towards the surface, resulting in blisters on the skin, generally on the distal lower extremity (foot). Within 72 hours, the blister ruptures, exposing one end of the emergent worm. The blister causes a very painful burning sensation as the worm emerges, and the sufferer will often immerse the affected limb in water to relieve the burning sensation. When a blister or open sore is submerged in water, the adult female releases hundreds of thousands of stage 1 guinea worm larvae, thereby contaminating the water.
During the next few days, the female worm can release more larvae whenever it comes in contact with water, as it extends its posterior end through the hole in the host’s skin. These larvae are eaten by copepods, and after two weeks (and two molts), the stage 3 larvae become infectious and, if not filtered from drinking water, will cause the cycle to repeat. Infected copepods can live in the water for up to four months.
The male guinea worm is typically much smaller (12–29 mm or 0.47–1.14 in) than the female, which, as an adult, can grow to 60–100 cm (2–3 ft) long and be as thick as a spaghetti noodle.
Infection does not create immunity, so people can repeatedly experience Dracunculiasis throughout their lives.
Hosts. Until recently humans and water fleas (Cyclops) were regarded as the only animals this parasite infects. It has been shown that baboons, cats, dogs, frogs and catfish (Synodontis) can also be infected naturally. Ferrets can be infected experimentally.
Prevention. Guinea worm disease can be transmitted only by drinking contaminated water, and can be completely prevented through two relatively simple measures: Prevent people from drinking contaminated water containing the Cyclops copepod (water flea), which can be seen in clear water as swimming white specks. Filter all drinking water, using a fine-mesh cloth filter like nylon, to remove the guinea worm-containing crustaceans. Regular cotton cloth folded over a few times is an effective filter. Filter the water through ceramic or sand filters. Boil the water. Develop new sources of drinking water without the parasites, or repair dysfunctional water sources. Treat water sources with larvicides to kill the water fleas.
Prevent people with emerging Guinea worms from entering water sources used for drinking.
Community-level case detection and containment is key. For this, staff must go door to door looking for cases, and the population must be willing to help and not hide their cases.
Immerse emerging worms in buckets of water to reduce the number of larvae in those worms, and then discard that water on dry ground. Discourage all members of the community from setting foot in the drinking water source. Guard local water sources to prevent people with emerging worms from entering.
Treatment. There is no vaccine or medicine to treat or prevent Guinea worm disease. Once a Guinea worm begins emerging, the first step is to do a controlled submersion of the affected area in a bucket of water. This causes the worm to discharge many of its larvae, making it less infectious. The water is then discarded on the ground far away from any water source. Submersion results in subjective relief of the burning sensation and makes subsequent extraction of the worm easier. To extract the worm, a person must wrap the live worm around a piece of gauze or a stick. The process can be long, taking anywhere from hours to a week. Gently massaging the area around the blister can help loosen the worm. This is nearly the same treatment that is noted in the famous ancient Egyptian medical text, the Ebers papyrus from 1550 BC. Some people have said that extracting a Guinea worm feels like the afflicted area is on fire. However, if the infection is identified before an ulcer forms, the worm can also be surgically removed by a trained doctor in a medical facility.
Although Guinea worm disease is usually not fatal, the wound where the worm emerges could develop a secondary bacterial infection such as tetanus, which may be life-threatening—a concern in endemic areas where there is typically limited or no access to health care. Analgesics can be used to help reduce swelling and pain and antibiotic ointments can help prevent secondary infections at the wound site. At least in the Northern region of Ghana, the Guinea worm team found that antibiotic ointment on the wound site caused the wound to heal too well and too quickly making it more difficult to extract the worm and more likely that pulling would break the worm. The local team preferred to use something called “Tamale oil” (after the regional capital) which lubricated the worm and aided its extraction.
It is of great importance not to break the worm when pulling it out. Broken worms have a tendency to putrefy or petrify. Putrefaction leads to the skin sloughing off around the worm. Petrification is a problem if the worm is in a joint or wrapped around a vein or other important area.
Use of metronidazole or thiabendazole may make extraction easier, but also may lead to migration to other parts of the body.
Epidemiology. In 1986, there were an estimated 3.5 million cases of Guinea worm in 20 endemic nations in Asia and Africa. Ghana alone reported 180,000 cases in 1989. The number of cases has since been reduced by more than 99.999% to 22 in 2015 — in the four remaining endemic nations of Africa: South Sudan, Chad, Mali and Ethiopia. This is the lowest number of cases since the eradication campaign began. As of 2010, however, the WHO predicted it will be “a few years yet” before eradication is achieved, on the basis that it took 6–12 years for the countries that have so far eliminated Guinea worm transmission to do so after reporting a similar number of cases to that reported in southern Sudan (now South Sudan) in 2009.
Certified free
Endemic countries must report to the International Commission for the Certification of Dracunculiasis Eradication and document the absence of indigenous cases of Guinea worm disease for at least three consecutive years to be certified as Guinea worm-free. The results of this certification scheme have been remarkable: by 2007, Benin, Burkina Faso, Chad, Côte d’Ivoire, Kenya, Mauritania, Togo, and Uganda had stopped transmission, and Cameroon, Central African Republic, India, Pakistan, Senegal, Yemen were WHO certified. Nigeria was certified as having ended transmission in 2013, followed by Ghana in 2015.
Since humans are the principal host for Guinea worm, and there is no evidence that D. medinensis has ever been reintroduced to humans in any formerly endemic country as the result of non-human infections, the disease can be controlled by identifying all cases and modifying human behavior to prevent it from recurring. Once all human cases are eliminated, the disease cycle will be broken, resulting in its eradication.
A significant change from 2014 is the increased effort being used to identify and treat infected dogs — mainly in Chad where the vast majority of cases of dogs hosting the worm have been found, but also significantly in Ethiopia. The August Carter Center report predicts that Chad may be the last country that eliminates dracunculiasis.
In 2016, 25 cases have been reported – 16 in Chad, six in South Sudan and three in Ethiopia. No cases were reported in Mali.
TRACHOMA Granular conjunctivitis, blinding trachoma, Egyptian ophthalmia
Trachoma is an infectious disease caused by bacterium Chlamydia trachomatis. The infection causes a roughening of the inner surface of the eyelids. This roughening can lead to pain in the eyes, breakdown of the outer surface or cornea of the eyes, and eventual blindness. Untreated, repeated trachoma infections can result in a form of permanent blindness when the eyelids turn inward.
The bacteria that cause the disease can be spread by both direct and indirect contact with an affected person’s eyes or nose. Indirect contact includes through clothing or flies that have come into contact with an affected person’s eyes or nose. Children spread the disease more often than adults. Poor sanitation, crowded living conditions, and not enough clean water and toilets also increase spread.
Efforts to prevent the disease include improving access to clean water and treatment with antibiotics to decrease the number of people infected with the bacterium. This may include treating, all at once, whole groups of people in whom the disease is known to be common. Washing, by itself, is not enough to prevent disease but may be useful with other measures. Treatment options include oral azithromycin and topical tetracycline. Azithromycin is preferred because it can be used as a single oral dose. After scarring of the eyelid has occurred, surgery may be required to correct the position of the eyelashes and prevent blindness.
Globally, about 80 million people have an active infection. In some areas, infections may be present in as many as 60–90% of children. Among adults, it more commonly affects women than men – likely due to their closer contact with children. The disease is the cause of decreased vision in 2.2 million people, of whom 1.2 million are completely blind. It commonly occurs in 53 countries of Africa, Asia, and Central and South America, with about 230 million people at risk. It results in US$8 billion of economic losses a year. It belongs to a group of diseases known as neglected tropical diseases.
Signs and symptoms. The bacterium has an incubation period of 5 to 12 days, after which the affected individual experiences symptoms of conjunctivitis, or irritation similar to “pink eye.” Blinding endemic trachoma results from multiple episodes of reinfection that maintains the intense inflammation in the conjunctiva. Without reinfection, the inflammation will gradually subside.
The conjunctival inflammation is called “active trachoma” and usually is seen in children, especially pre-school children. It is characterized by white lumps in the undersurface of the upper eyelid (conjunctival follicles or lymphoid germinal centres) and by non-specific inflammation and thickening often associated with papillae. Follicles may also appear at the junction of the cornea and the sclera (limbal follicles). Active trachoma will often be irritating and have a watery discharge. Bacterial secondary infection may occur and cause a purulent discharge.
The later structural changes of trachoma are referred to as “cicatricial trachoma”. These include scarring in the eyelid (tarsal conjunctiva) that leads to distortion of the eyelid with buckling of the lid (tarsus) so the lashes rub on the eye (trichiasis). These lashes will lead to corneal opacities and scarring and then to blindness. Linear scar present in the Sulcus subtarsalis is called Arlt’s line (named after Carl Ferdinand von Arlt). In addition, blood vessels and scar tissue can invade the upper cornea (pannus). Resolved limbal follicles may leave small gaps in pannus (Herbert’s Pits).
Most commonly children with active trachoma will not present with any symptoms as the low-grade irritation and ocular discharge is just accepted as normal. However, further symptoms may include: Eye discharge, Swollen eyelids, Trichiasis (turned-in eyelashes), Swelling of lymph nodes in front of the ears, Sensitivity to bright lights, Increased heart rate, Further ear, nose and throat complications. The major complication or the most important one is corneal ulcer occurring due to rubbing by concentrations, or trichiasis with superimposed bacterial infection.
Cause. Trachoma is caused by Chlamydia trachomatis, serotypes (serovars) A, B, and C. It is spread by direct contact with eye, nose, and throat secretions from affected individuals, or contact with fomites (inanimate objects that carry infectious agents), such as towels and/or washcloths, that have had similar contact with these secretions. Flies can also be a route of mechanical transmission. Untreated, repeated trachoma infections result in entropion, the inward turning of the eyelids, which may result in blindness due to damage to the cornea. Children are the most susceptible to infection due to their tendency to easily get dirty, but the blinding effects or more severe symptoms are often not felt until adulthood.
Blinding endemic trachoma occurs in areas with poor personal and family hygiene. Many factors are indirectly linked to the presence of trachoma including lack of water, absence of latrines or toilets, poverty in general, flies, close proximity to cattle, crowding, and so forth. However, the final common pathway seems to be the presence of dirty faces in children that facilitates the frequent exchange of infected ocular discharge from one child’s face to another. Most transmission of trachoma occurs within the family.
Diagnosis. McCallan’s classification: Stage 1 (Incipient trachoma). Stage 2 (Established trachoma). Stage 3 (Cicatrising trachoma). Stage 4 (Healed trachoma)
Hyperaemia of palpebral conjunctive. Appearance of mature follicle & papillae. Scarring of palpebral conjunctiva. Disease is cured or is not markable. Immature follicle. Progressive corneal pannus. Scars are easily visible as white bands. Sequelae to cicatrisation cause symptoms
WHO classification (a simplified grading system for trachoma):
Trachomatous inflammation, follicular (TF)—Five or more follicles of >0.5 mm on the upper tarsal conjunctiva
Trachomatous inflammation, intense (TI)—Papillary hypertrophy and inflammatory thickening of the upper tarsal conjunctiva obscuring more than half the deep tarsal vessels
Trachomatous scarring (TS)—Presence of scarring in tarsal conjunctiva.
Trachomatous trichiasis (TT)—At least one ingrown eyelash touching the globe, or evidence of epilation (eyelash removal)
Corneal opacity (CO)—Corneal opacity blurring part of the pupil margin
Prevention. Although trachoma was eliminated from much of the developed world in the 20th century, this disease persists in many parts of the developing world, particularly in communities without adequate access to water and sanitation.
Environmental measures. Modifications in water use, fly control, latrine use, health education, and proximity to domesticated animals have all been proposed to reduce transmission of C. trachomatis and ultimately impact on the transmission of ocular infection by means of lack of facial cleanliness.
A systematic review examining the effectiveness of environmental sanitary measures on the prevalence of active trachoma in endemic areas showed that usage of insecticide spray resulted in significant reductions of trachoma and fly density in some studies. Health education also resulted in reductions. Improved water supply did not result in a reduction of trachoma incidence.
Antibiotics. Community-based, mass antibiotic treatment when the prevalence of active trachoma among one- to nine-year-old children is greater than 10 percent. Subsequent annual treatment should be administered for three years, at which time the prevalence should be reassessed. Annual treatment should continue until the prevalence drops below five percent. At lower prevalences, antibiotic treatment should be family-based.
Management.
Antibiotics. Azithromycin (single oral dose of 20 mg/kg) or topical tetracycline (one percent eye ointment twice a day for six weeks). Azithromycin is preferred because it is used as a single oral dose. Although it is expensive, it is generally used as part of the international donation program organized by Pfizer through the International Trachoma Initiative. Azithromycin can be used in children from the age of six months and in pregnancy. As a community-based antibiotic treatment, some evidence suggests that oral azithromycin was more effective than topical tetracycline; however, there was no consistent evidence that supported oral or topical antibiotics as being more effective.
Surgery. With trichiasis, a bilamellar tarsal rotation procedure is warranted to direct the lashes away from the globe. Evidence suggests that usage of a lid clamp and absorbable sutures would result in reduced lid contour abnormalities and granuloma formulation post-surgery. Early intervention is beneficial as the rate of recurrence is higher in more advanced disease.
Epidemiology. As of 2008, between 40–80 million people are infected, and between 1.3 million and 8 million have permanent blindness due to trachoma. It is common in more than 50 countries worldwide. In many of these communities, women are three times more likely than men to be blinded by the disease, due to their roles as caregivers in the family. About 110 million people live in endemic areas and need treatment. An additional 210 million live where trachoma is suspected endemic.
Ghana, Mexico, Saudi Arabia, Iran, Morocco and Oman report that the disease nationally eliminated. Australia is the only developed country to still have endemic blinding trachoma. In 2008, trachoma was found in half of Australia’s very remote communities at endemic levels.
The WHO has set a target to eliminate trachoma as a public health problem by 2020. The International Coalition for Trachoma Control (ICTC) has produced a strategic plan called 2020 INSight that lays out actions and milestones to achieve global elimination of blinding trachoma by the year 2020.
Etymology. The term is derived from New Latin trāchōma, from Greek τράχωμα trākhōma, from τραχύς trākhus “rough.”