Neglected tropical diseases
Dangerous, debilitating, and chronic infections add to the burden of people already disadvantaged by poverty in tropical regions of the world; and, as they are particular to these regions, investment in new drugs to combat them has been a problem. While malaria, HIV/AIDS, and tuberculosis are well known, with substantive efforts to prevent and control these infections in communities, there are many lesser known infections that cause persistent morbidity. “Neglected tropical diseases” are the tropical infections once the “big three” have been taken out, and a vocal group of organizations and people are promoting research, development, and control programmes, of these conditions1.
The actual scope of neglected tropical diseases varies depending on the source. For the World Health Organization, they are clearly defined on their website2. Other groups include other diseases, and the journal PLOS Neglected Tropical Diseases has promoted a more inclusive list3 (which we have adopted), but the theme is the same: tropical diseases associated with poverty that cause severe disability, life-long impairments, and death; with an estimated one billion people (“the bottom billion”) infected.
Key to tackling neglected tropical diseases is clear evidence that the drug to treat or prevent is effective; analysis of comparative effects, particularly, with some drugs, in relation to adverse effects; and evaluation of the effectiveness of programmes that deliver them. Cochrane Reviews are an important independent analysis of research relevant to disease control in neglected tropical diseases, and this collection brings together the completed Cochrane Reviews that have been prepared on the effects of a variety of interventions to prevent and treat several neglected tropical diseases. Several Cochrane Review Groups have prepared relevant reviews, including the Cochrane Infectious Diseases Group, and the Cochrane Skin Group.
Amoebiasis
Amoebic colitis is caused by the parasite Entamoeba histolytica. This protozoan is distributed throughout the world and is commonly acquired by ingestion of contaminated food or water. It is estimated that about 40 to 50 million people infected with E. histolytica develop amoebic colitis or extraintestinal abscesses, which result in up to 100,000 deaths per year. Adequate therapy for amoebic colitis is necessary to reduce the severity of illness, prevent development of complicated disease and extraintestinal spread, and decrease transmission.
Antiamoebic drugs for treating amoebic colitis
Metronidazole is currently the drug of choice for treating invasive amoebiasis in adults and children, but it may not be sufficient to eliminate parasite cysts in the intestine. Combinations with other drugs are therefore also used. Also, some unpleasant adverse effects associated with metronidazole in some patients, and the possibility of parasite resistance to metronidazole has to be considered. This review evaluates antiamoebic drugs for treating amoebic colitis.
The most common complication of amoebiasis is the formation of a pus-filled mass inside the liver (liver abscess). Metronidazole is the drug of choice for treatment of amoebic liver abscesses, and this is followed by a luminal agent to eradicate the asymptomatic carrier state. However, a subset of patients with amoebic liver abscesses remains symptomatic, with a significant risk of rupture of the abscess into the peritoneum. The role of image-guided percutaneous therapeutic aspiration in these patients remains controversial. This review assesses the beneficial and harmful effects of image-guided percutaneous procedure plus metronidazole versus metronidazole alone in patients with uncomplicated amoebic liver abscess.
Chagas disease (American trypanosomiasis)
Chagas disease is the result of human infection by the parasite Trypanosoma cruzi. The disease is endemic in many Latin American countries, with an estimated 13 million people infected.4 Triatomine insects, which live in cracks and crevices of poor-quality houses, emerge at night to bite and feed on blood of humans, transmit the parasites as they feed.
Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection
About 30% of people infected with Trypanosoma cruzi go on develop a major heart disease in their 30s or 40s, after decades of silent infection. This review assesses the effects of trypanocidal therapy for chronic asymptomatic Trypanosoma cruzi infections.
Trypanocidal drugs for late stage, symptomatic Chagas disease (Trypanosoma cruzi infection)
People with Chagas disease may develop progressive and potentially lethal heart conditions. This review assesses the harms and benefits of nitrofurans and imidazolic trypanocidal drugs for treating late-stage chronic Chagas disease and chronic Chagasic cardiopathy (characterized by heart failure with bizarre rhythm and/or conduction defect).
Cholera
Cholera is caused by bacteria ingested through contaminated food or water and is commonly found where sanitation measures are poor. It causes severe diarrhoea and vomiting, which can lead to profound dehydration and potentially death.
Reduced osmolarity oral rehydration solution for treating cholera
Oral rehydration solution (ORS) is an effective treatment for diarrhoea, but ORS with lower electrolyte content is safe and more effective in people with non-cholera diarrhoea. As cholera causes rapid electrolyte loss, it is important to know if these benefits are similar for people with cholera. This review compares the safety and efficacy of reduced osmolarity ORS with standard ORS for treating diarrhoea due to cholera.
Vaccines for preventing cholera: killed whole cell or other subunit vaccines (injected)
Oral cholera vaccines are newer alternatives to the parenteral vaccines that have been thought to confer only moderate and short-term immunity. This review assesses the effect of cholera vaccines in preventing cases of cholera and preventing deaths. However, this review is in the process of being updated and will be divided split into two separate Cochrane Reviews: 'Oral vaccines for cholera' and 'Vaccines for preventing cholera: killed whole cell or other subunit vaccines (injected)'.
Dengue/dengue haemorrhagic fever
Corticosteroids for treating dengue shock syndrome
Dengue virus is an arbovirus transmitted to humans by two species of mosquito, Aedes aegypti and A. albopictus. The four serotypes of dengue virus can cause a wide range of symptoms from mild febrile illness to dengue haemorrhagic fever (severe illness with fever and bleeding), which leads to dengue shock syndrome (shock, collapse, and sometimes death). It is currently estimated that most of the 100 million cases of dengue infection occurring annually are in South-East Asia, although many also occur in the Americas. Dengue shock syndrome is the most severe form of dengue haemorrhagic fever. The current treatment for dengue shock syndrome is to give fluids directly into the bloodstream, but corticosteroids have been suggested as drugs that may help due to their anti-inflammatory properties. This review compares corticosteroids with placebo or no corticosteroids for treating dengue shock syndrome.
Hydatid disease (echinococcosis)
Hepatic hydatid cyst disease (cystic echinococcosis) is an important public health problem in parts of the world where dogs are used for cattle breeding. Management of uncomplicated hepatic hydatid cysts is currently surgical. However, the puncture, aspiration, injection, and re-aspiration (PAIR) method with or without benzimidazole coverage has appeared as an alternative to surgery since the mid-1990s. This review assesses the benefits and harms of PAIR with or without benzimidazole coverage for patients with uncomplicated hepatic hydatid cyst in comparison with sham/no intervention, surgery, or medical treatment.
Japanese encephalitis
Vaccines for preventing Japanese encephalitis
Japanese encephalitis is a viral disease of the central nervous system with general symptoms of headache, fever, vomiting, and diarrhoea. Most people recover within a week without further complications, but approximately 1 in 300 suffers additional and severe symptoms such as disorientation, seizures, paralysis, and coma. Around thirty per cent of the severe cases are fatal, and most survivors are left with serious and often chronic disabilities such as mental impairment, limb paralysis, and blindness. Vaccination is recognized as the only practical measure for preventing Japanese encephalitis, but production shortage, costs, and issues of licensure impair vaccination programmes in many affected countries. Concerns over vaccine effectiveness and safety also have a negative impact on acceptance and uptake. This review evaluates vaccines for preventing Japanese encephalitis in terms of effectiveness, adverse events, and immunogenicity.
Leishmaniasis: visceral & cutaneous
The leishmaniases are a group of diseases caused by protozoan parasites of the genus Leishmania. The parasites are transmitted by bites from infected female sandflies. Leishmaniases are common in many tropical and subtropical developing countries, with an estimated 12 million people infected and 350 million people at risk.4 Leishmaniasis presents in three main clinical forms that are associated with a broad range of signs, symptoms, and degrees of severity: cutaneous leishmaniasis affects the skin and mucous membranes; mucocutaneous leishmaniasis is a chronic form seen in South America that also affects the mucous membranes, particularly the nose, throat, and mouth; and visceral leishmaniasis affects internal organs, especially the spleen, liver, bone marrow, and lymph nodes.
Interventions for American cutaneous and mucocutaneous leishmaniasis
Pentavalent antimonial drugs are the most prescribed treatment for American cutaneous and mucocutaneous leishmaniasis. Other treatments have been used because these are expensive, toxic, and painful, and because resistance is emerging. This review assesses the effects of therapeutic interventions for American cutaneous and mucocutaneous leishmaniasis.
Interventions for Old World cutaneous leishmaniasis
Cutaneous leishmaniasis is a disfiguring and stigmatising disease occurring in areas of the Mediterranean, Middle East, and Asia. Many treatments have been used, but the pentavalent antimonial drugs have been used since the 1940s as the main first-line therapeutic agents. This review assesses the effects of treatments for Old World cutaneous leishmaniasis.
Leprosy
Leprosy is a chronic infectious disease caused by the bacillus Mycobacterium leprae. The disease spreads through tiny droplets from the nose or mouth from infected and untreated individuals, and it develops when the immune system fails to respond effectively. The infection causes nerve damage which can result in nerve function impairment and disability.
Corticosteroids for treating nerve damage in leprosy
Leprosy causes nerve damage that can result in nerve function impairment and disability. Corticosteroids are commonly used for treating nerve damage, although the long-term effect is uncertain. This review assesses the effects of corticosteroids on nerve damage in leprosy.
Decompressive surgery for treating nerve damage in leprosy
Decompressive surgery is used for treating the nerve damage associated with leprosy. Because of uncertainties around this intervention, this review assesses the effects of decompressive surgery on nerve damage in leprosy.
Interventions for erythema nodosum leprosum
Erythema nodosum leprosum is a serious immunological complication of leprosy, causing inflammation of skin, nerves, other organs, and general malaise. Many different therapies exist, but it is unclear if they work or which therapy is optimal. This review assesses the effects of interventions for erythema nodosum leprosum to establish which treatments are most beneficial.
Interventions for skin changes caused by nerve damage in leprosy
The main complication of sensory nerve damage with leprosy is neuropathic ulceration, particularly of the feet. This review explores interventions that can prevent and treat secondary damage to skin and limbs in people affected by leprosy.
Leptospirosis
Antibiotic prophylaxis for leptospirosis
Leptospira infection is a global zoonosis caused by spirochetes of the genus Leptospira. It causes endemic disease among agricultural workers and others regularly exposed to flooded fields and livestock, or other sources of animal urine. Outbreaks of leptospirosis also occur among immune-naive individuals who may be exposed because of changing environmental conditions, travel, or occupational or recreational activities, for example. This review assesses the evidence for or against use of antibiotic prophylaxis against Leptospira infection.
Lymphatic filariasis
Lymphatic filariasis is a parasitic infection of threadlike, filarial worms. It is spread by female mosquitoes and affects about 120 million people.4 The infection can cause severe disability due to the clinical symptoms and signs that include hydrocoele (excess fluid inside the scrotal sac), lymphoedema (swelling and enlargement of affected areas of the body), and elephantiasis (long-standing enlargement and swelling of the limbs, scrota, or breasts associated with skin thickening). Bancroftian filariasis, caused by Wuchereria bancrofti, occurs in tropical regions of Africa, Asia, China, Pacific Islands, the Caribbean and South America. Brugian filariasis is less common and occurs in parts of Asia (caused by Brugia malayi) and Indonesia (caused by B. timori).
Albendazole for lymphatic filariasis
Mass treatment with albendazole co-administered with another antifilarial drug is part of a global programme to eliminate lymphatic filariasis. This is because the disease can not only cause visible infection, but because many infected people have no symptoms but do contribute to the perpetuation of the infection in the community. This review summarizes the effects of albendazole alone or in combination with antifilarial drugs for clinical treatment and community control of lymphatic filariasis.
Diethylcarbamazine (DEC)-medicated salt for community-based control of lymphatic filariasis
Mass treatment with diethylcarbamazine (DEC)-medicated salt has been used in a number of places as a control measure for lymphatic filariasis. This review looks at the effectiveness of giving entire communities DEC-medicated salt and aims to evaluate its effects on infection with lymphatic nematodes.
Neurocysticercosis
Anthelmintics for people with neurocysticercosis
Neurocysticercosis is an infection of the central nervous system by the larval stage of the pork tapeworm Taenia solium. If eggs (cysticerci) from the faeces of humans infected with the intestinal parasites are ingested, they can migrate from the gut to lodge in various tissues of the body, where they form cysts (cysticercosis). This review is confined to treating neurocysticercosis, where the cysts lodge in the brain. Some people may have no symptoms if this happens, but others may suffer from seizures, headaches, or more rarely from confusion, loss of balance, or brain swelling. More rarely still, someone may die. Neurocysticercosis is mainly found where people live in close contact with pigs and where the sanitation is poor. It affects around 50 million people worldwide, and in some areas is the leading cause of adult-onset epilepsy. Two drugs, praziquantel and albendazole, can be used specifically in neurocysticercosis to help kill the parasite; these drugs are known as anthelmintics. This review assesses the effectiveness and safety of anthelmintics for people with neurocysticercosis.
Onchocerciasis (river blindness)
Ivermectin for onchocercal eye disease (river blindness)
Onchocerciasis causes severe itching and thickening of the skin, and damages structures at the front and back of the eye as well as affects the nerve that connects the eye with the brain. It is caused by tiny worms that are transmitted from person to person by a small biting fly. The fly breeds in fast flowing rivers and streams mainly in West Africa, although it is also endemic in some countries in the Americas and Eastern Mediterranean. It is believed that ivermectin (a microfilaricide) could prevent blindness due to onchocerciasis. This review assesses the effectiveness of ivermectin in preventing visual impairment and visual field loss in onchocercal eye disease.
Paracoccidioidomycosis
Drugs for treating paracoccidioidomycosis
Paracoccidioidomycosis is a fungal infection that causes ulcers, swelling, fever, and pain. If it also gets into the lungs, it can produce coughing, shortage of breath, chest pain, weight loss, and sometimes death. Without treatment, those suffering this disease may die in a few months or years. Paracoccidioidomycosis is found in particular geographic localities in Latin America. This review evaluates drugs used for treating paracoccidioidomycosis.
Salmonellosis
Antibiotics for treating salmonella gut infections
Non-typhoidal salmonella appears to be an important cause of acute diarrhoea in some developing countries. Antibiotic treatment of salmonella infections aims to shorten illness and prevent serious complications. There are also concerns about increasing antibiotic drug resistance. This review assesses the effects of antibiotics in adults and children with diarrhoea who have salmonella.
Vaccines for preventing invasive salmonella infections in people with sickle cell disease
Salmonella infections are a common bacterial cause of invasive disease in people with sickle cell disease especially children, and are associated with high morbidity and mortality rates. Although available in some centres, people with sickle cell anaemia are not routinely immunized with salmonella vaccines. This review determines whether routine administration of salmonella vaccines to people with sickle cell disease reduces the morbidity and mortality associated with infection.
Scabies
Interventions for treating scabies
Scabies is an intensely itchy parasitic infection of the skin caused by the Sarcoptes scabiei mite. The female mite burrows into the skin to lay eggs, which then hatch out and multiply. The infection can spread from person to person via direct skin contact, including sexual contact. Scabies occurs throughout the world, but it is particularly problematic in areas of poor sanitation, overcrowding, and social disruption, and is endemic in many resource-poor countries. Various drugs have been developed to treat scabies, and herbal and traditional medicines are also used. This review evaluates topical and systemic drugs for treating scabies.
Schistosomiasis
Drugs for treating urinary schistosomiasis
Urinary schistosomiasis is caused by the blood fluke, Schistosoma haematobium, which is transmitted when people from contact with contaminated water. The worms reside in blood vessels of the bladder and cause urinary schistosomiasis, which can lead to long-term ill-health. The disease is commonly found in African and eastern Mediterranean countries, especially in poor, rural areas. This review evaluates antischistosomal drugs, used alone or in combination, for treating urinary schistosomiasis.
Interventions for treating schistosomiasis mansoni
Schistosoma mansoni is a parasite carried by freshwater snails. Human infection occurs from contact with contaminated water. The worms travel to the intestine, liver, and spleen, and can be fatal. The disease occurs in the tropics, including countries in South America, the Caribbean, Africa, and the eastern Mediterranean. This review assesses the effects of using oxamniquine and praziquantel for treating S. mansoni infection.
Shigellosis
Antibiotic therapy for Shigella dysentery
Shigellosis is a bacterial infection of the colon that can cause diarrhoea and dysentery (diarrhoea with blood and/or mucus), and may lead to death. It occurs mainly in low- and middle-income countries where overcrowding and poor sanitation exist, and may lead to around 1.1 million deaths per year globally, mostly in children aged less than five years. Mild symptoms are self-limiting but in more severe cases, antibiotics are recommended for cure and preventing relapse. The antibiotics recommended are diverse, have regional differences in sensitivity, and have adverse effects. This review evaluates the efficacy and safety of antibiotics for treating Shigella dysentery.
Sleeping sickness (Human African trypanosomiasis)
Chemotherapy for second-stage Human African trypanosomiasis
Human African trypanosomiasis (sleeping sickness) is parasitic disease transmitted through the bite of infected tsetse flies. Sleeping sickness is a painful and protracted disease, and is considered invariably fatal without adequate treatment. The disease occurs throughout the area where tsetse flies are found in 36 sub-Saharan countries, with over 60 million people at risk of infection and an estimated 300,000 individuals infected. Treatment of infected individuals is crucial for reducing the trypanosome reservoir in humans and consequently for controlling the disease. This review evaluates the effectiveness and safety of drugs for treating second-stage human African trypanosomiasis.
Snake bite
Interventions for preventing reactions to snake antivenom
People can die or can be seriously disabled after being bitten by a venomous snake. Antivenom is used to neutralize snake bite toxins in people showing evidence of envenomation. It is made from animal sera, and adverse effects, including life-threatening anaphylaxis, are common. This review assesses the effects of drugs given routinely with snake antivenom to prevent adverse effects.
Soil-transmitted helminthiasis
More than a quarter of the world's population is estimated to be infected with one or more of the most common soil-transmitted intestinal worms (nematode geohelminths). These include roundworms (Ascaris lumbricoides), hookworms (Necator americanus and Ancylostoma duodenale), and whipworms (Trichuris trichura). Infections are widely distributed in tropical and subtropical areas, and most infected people harbour multiple species. The burden of disease falls disproportionately on the poor, where inadequate sanitation, overcrowding, low levels of education, and lack of access to health care make them particularly susceptible.
In areas where intestinal worm infections occur, the World Health Organization recommends treating all school children at regular intervals with deworming drugs to improve growth and school performance. This review summarizes the effects of deworming drugs used to treat soil-transmitted intestinal worms (nematode geohelminths) on growth and school performance in children.
Deworming helminth co-infected individuals for delaying HIV disease progression
The HIV-1 pandemic has disproportionately affected individuals in resource-constrained settings where other infectious diseases, such as helminth infections, also are highly prevalent. There are biologically plausible reasons for possible effects of helminth infection in HIV-1-infected individuals, and findings from multiple studies suggest that helminth infection may adversely affect HIV-1 progression. This review evaluates whether if treating helminth infection in individuals with HIV-1 can reduce the progression of HIV-1 as determined by changes in CD4 count, viral load, or clinical disease progression.
Effect of administration of antihelminthics for soil-transmitted helminths during pregnancy
Intestinal worms (helminths) contribute to iron deficiency anaemia as they feed on blood and cause further bleeding by releasing anticoagulant compounds. They also affect the supply of nutrients and cause anorexia, vomiting, and diarrhoea. Pregnancy complicated by maternal hookworm infection poses a serious threat to the health of mothers and their babies, especially in developing countries. Antihelminthics are highly efficacious in treating hookworm, but evidence of their beneficial effect and safety when given during pregnancy has not been established. The review evaluates the effects of the administration of antihelminthics for soil-transmitted helminths during the second or third trimester of pregnancy on maternal anaemia and pregnancy outcomes.
Syphilis
Antibiotics for syphilis diagnosed during pregnancy
Syphilis is a potentially fatal, sexually transmitted disease that passes from a pregnant woman to her unborn baby. If the woman is untreated, the fetus may be aborted or her baby may be born with the disease, suffer permanent disability, and be disfigured. The effectiveness of penicillin in curing infection with syphilis in pregnant women and preventing the baby being born with congenital syphilis was established soon after its introduction in the 1940s and before the widespread use of randomized controlled trials. Although rare in developed countries, the incidence of syphilis is high and increasing in many developing countries, particularly where HIV/AIDS is common. This review assesses antibiotic treatment regimens (in terms of dose, length of course, and mode of administration) for pregnant women with syphilis and with and without concomitant infection with HIV.
Trachoma
Trachoma is the world's leading cause of preventable blindness. It is a bacterial infection in the eye caused by Chylamydia trachomatis and is common in underprivileged children living in the poor communities of low-income countries, mainly in Africa, Asia, and the Middle East. Through repeated infections, the eyelashes turn in and brush against the cornea. The contact between the lashes and the surface of the eye results in blindness.
In 1997, the World Health Organization launched an initiative on trachoma control based on the 'SAFE' strategy (surgery, antibiotics, facial cleanliness, and environmental improvement). This review aims to assess the evidence supporting the antibiotic arm of the SAFE strategy by assessing the effects of antibiotics on both active trachoma and on Chlamydia trachomatis infection of the conjunctiva.
Environmental sanitary interventions for preventing active trachoma
One of the major strategies advocated for the control of the trachoma is the application of various environmental sanitary measures to such communities. Environmental sanitation is a package of measures aimed at eliminating factors that encourage proliferation of flies and the spread of the disease. Some of these interventions include provision of water and latrines as well insecticide spray to control flies. This review assesses the evidence for the effectiveness of environmental sanitary measures on the prevalence of active trachoma in endemic areas.
Face washing promotion for preventing active trachoma
Face washing is part of the 'SAFE' strategy (surgery, antibiotics, facial cleanliness, and environmental improvement) promoted by the World Health Organization programme for the global elimination of trachoma. Face washing should reduce the number of eye-seeking flies and transmission of the trachoma organism from person-to-person. This review assesses the effects of face washing on the prevalence of active trachoma in endemic communities.
Interventions for trachoma trichiasis
Repeated infections cause scarring of the conjunctiva of the upper eyelid, which causes the eyelid to turn in (entropion) so that the eyelashes touch the cornea at the front of the eye. This is known as trachoma trichiasis. Every movement of the eye or eyelids causes trauma to the corneal surface so that it eventually turns opaque and the person becomes blind. This review assesses the effects of different interventions for trachoma trichiasis (both surgical and non-surgical) to identify the most effective means of eliminating trichiasis and the most acceptable way of delivering it.
Acknowledgements
Lucie Osbourn for drafting the text; and the Cochrane Infectious Diseases Group for comments and edits.
References
1Hotez PJ, Fenwick A, Savioli L, Molyneux DH. Rescuing the bottom billion through control of neglected tropical diseases. The Lancet. 2009;373(9674):1570-5.
2World Health Organization. Diseases covered by the NTD Department. www.who.int/neglected_diseases/diseases/en/ (accessed 5 August 2010).
3PLoS Neglected Tropical Diseases Journal Scope. www.plosntds.org/static/scope.action (accessed 5 August 2010).
4World Health Organization. Neglected tropical diseases: Which diseases are most common? www.who.int/neglected_diseases/faq/en/index6.html (accessed 5 August 2010).
Image credit: Mauro Fermariello/Science Photo Library, M155/568
Date published: 9 August 2010; updated 10 September 2010 to edit text in the neurocysticercosis section
Contact: Cochrane Editorial Unit (editorial-unit@cochrane.org)
