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Neglected tropical diseases: the top five

Special Collection
Dangerous, debilitating, and chronic infections add to the burden of people disadvantaged by poverty in tropical regions of the world. 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. As these neglected tropical diseases (NTDs) are particular to these regions, the lack of investment in new drugs to combat them has been a problem.
This Cochrane Special Collection includes the top five causes of morbidity: diarrhoeal disease, food-borne trematodiases, lymphatic filariasis, schistosomiasis, and soil-transmitted helminthiases. 

Defining neglected tropical diseases
The scope of ‘neglected tropical diseases’ has developed over time, and its definition varies. The term did not exist within the published literature indexed on MEDLINE prior to 2005; citations rose rapidly to 86 in 2011.[1] Initially it referred to diseases where there was little private investment in the development of new drugs and thus required public investment; the term quickly encompassed diseases that occurred in the tropics in poor people. Some of these diseases were amenable to control by mass drug treatments. The World Health Organization (WHO) created the Department of Control of Neglected Tropical Diseases in 2005, and since then has been using a broadly consistent definition, which states that NTDs are "a diverse group of communicable diseases that prevail in tropical and subtropical conditions in 149 countries and affect more than one billion people, costing developing economies billions of dollars every year".[2] The WHO refers specifically to a list of 17 diseases
However, as the WHO acknowledges, "there are still many tropical, poverty-related diseases that affect the same populations and share many features with the neglected tropical diseases".[2] The criteria used to determine which diseases are included or excluded from this list are difficult to tease out.
A recent article by Horstick et al in PLOS Neglected Tropical Diseases provides a set of disease characteristics that are common to all currently used definitions.[3] This includes occurrence of diseases in the tropics or subtropics; neglected public health attention; neglected research and development in spending and in effective interventions; and affecting exclusively poor populations.
PLOS Neglected Tropical Diseases has promoted a more inclusive list, including over 30 conditions, and also allows for consideration of other infectious diseases on a ‘case-by-case’ basis.[4] This Special Collection and the Cochrane Library browse follow this approach.
The role of Cochrane
There is a lack of reliable evidence for interventions for the prevention and treatment of NTDs. This evidence can potentially result in large health gains for the world’s poorer populations. Particular attention needs to be paid to drugs with severe or common adverse effects. Evidence may come from analyses of comparative effects of drugs balancing benefits against harms, or evaluation of the effectiveness of programmes that deliver them.
Cochrane Reviews are an important independent analysis of research relevant to disease control in NTDs. This Special Collection brings together reviews from Cochrane Review Groups including Cochrane Infectious Diseases, Cochrane Eyes and Vision, and Cochrane Skin; and focuses on the effects of a variety of interventions to prevent and treat the top five groups of NTDs, according to the Global Burden of Disease study 2013 (causing the highest number of years lived with disability).[5] These include diarrhoeal disease, soil-transmitted helminthiases, food-borne trematodiases, schistosomiasis, and lymphatic filariasis. Currently, there are no Cochrane Reviews relating to food-borne trematodiases, highlighting the need for further research in this area.

Diarrhoeal disease: enteric pathogens (Shigella, Salmonella, Escherichia coli)

Enteric diseases include diarrhoeal and gut infections caused by identifiable bacteria, with the formal medical definition being “the passage of 3 or more unformed stools per day and any documented intestinal infection associated with disrupted intestinal absorptive and/ or barrier function” [6]. Shigella are a group of bacteria causing shigellosis, usually presenting with fever, stomach cramps, and diarrhoea. Escherichia coli are a diverse group of bacteria which are found in the environment, food, and intestines of both people and animals, and can infect the colon, urinary tract and respiratory system, amongst others. There are many different types of Salmonella bacteria; examples include serotype Thyphimurium and serotype Enteritidis. Like shigellosis, infection is typically accompanied with fever, stomach cramps, and diarrhoea.
Free Access
Antibiotic therapy for Shigella dysentery
Shigellosis is a bacterial infection of the colon that causes diarrhoea and can lead to death. 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 side effects. This review aims to evaluate the efficacy and safety of antibiotics for treating Shigella dysentery.
Interventions for haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura
Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are related conditions with similar clinical features of variable severity. HUS usually affects young children; the most common type is associated with diarrhoea due to infection with a Shiga toxin producing Escherichia coli or Shigella dysenteriae. This review evaluates the benefits and harms of different interventions for HUS and TTP separately, in people of all ages.
Free Access
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 aims to determine whether routine administration of salmonella vaccines to people with sickle cell disease reduces the morbidity and mortality associated with infection.
Free Access
Antimicrobials for treating symptomatic non‐typhoidal Salmonella infection
Non-typhoidal Salmonella (NTS) commonly causes diarrhoea, and is usually self-limiting, although sometimes people become ill with sepsis and dehydration. Routine antibiotic use for this infection could result in persistent colonization and the spread of resistant bacterial strains. This review aims to assess the efficacy and safety of giving antibiotics to people with non-typhoidal Salmonella diarrhoea.
Open Access
Vaccines for preventing typhoid fever
Typhoid fever and paratyphoid fever are important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Vaccination against typhoid fever is a key control measure; two typhoid vaccines are commercially available, Ty21a (oral) and Vi polysaccharide (parenteral), but neither is used routinely. This review aims to evaluate the efficacy and adverse effects of vaccines used to prevent typhoid fever.
Open Access
Polymer‐based oral rehydration solution for treating acute watery diarrhoea
Oral rehydration solution (ORS) is used to treat the dehydration caused by diarrhoeal diseases. Many different forms exist. Since 2004, the World Health Organization has recommended the osmolarity < 270 mOsm/L (ORS ≤ 270 ) (a measure of solute concentration) over the > 310 mOsm/L formulation (ORS ≥ 310). Glucose polymer-based ORS (eg prepared using rice or wheat) slowly releases glucose and may be superior. This review aims to compare polymer-based ORS with glucose-based ORS for treating acute watery diarrhoea.

Diarrhoeal disease: cholera

Cholera is caused by infection with the bacterium Vibrio cholerae, which is ingested through contaminated food or water and commonly found where sanitation measures are poor. It causes acute watery diarrhoea and vomiting, which can be severe and may lead to profound dehydration and potentially death.
Open Access
Antimicrobial drugs for treating cholera
Effective management of cholera requires early diagnosis and rehydration using oral rehydration salts or intravenous fluids. This review aims to quantify the benefit of antimicrobial treatment for patients with cholera, and determine whether there are differences between classes of antimicrobials or dosing schedules.
Oral vaccines for preventing cholera
Widespread use of cholera vaccines began in the 1960s. Two main types of oral vaccines have been investigated in clinical trials: inactivated vaccines (containing killed whole cells of Vibrio cholerae), and live attenuated vaccines (containing genetically modified, non-pathogenic strains of V. cholerae). This review assesses the effectiveness and safety of oral cholera vaccines in preventing cases of cholera and deaths from cholera.
Free Access
Vaccines for preventing cholera: killed whole cell or other subunit vaccines (injected)
Injected cholera vaccines are rarely used today, although they may have some benefit. It is valuable to summarize the evidence for effectiveness of injected cholera vaccines for comparison with newer oral vaccines. This review evaluates killed whole cell (KWC) cholera vaccines and other inactive subunit vaccines (administered by injection) for preventing cholera and death, and to evaluate the adverse effects.

Diarrhoeal disease: giardiasis

Giardia is an anaerobic flagellated protozoan parasite also known as Giardia intestinalis, Giardia lamblia, or Giardia duodenalis. It is spread by ingestion of cysts which can be found on surfaces or in soil, food, or water contaminated with faeces from infected humans or animals. Clinically it may be asymptomatic, or can cause diarrhoea, gas or flatulence, abdominal pain, nausea and dehydration.
Drugs for treating giardiasis
Giardiasis is usually treated with metronidazole given three times daily for five to 10 days. This review aims to evaluate the relative effectiveness of alternative antibiotic regimens for treating adults or children with symptomatic giardiasis.

Diarrhoeal disease: amoebiasis

Free Access
Antiamoebic drugs for treating amoebic colitis
Amoebic colitis is caused by the parasite Entamoeba histolytica, a protozoan distributed throughout the world and commonly acquired by ingestion of contaminated food or water. Adequate therapy for amoebic colitis is necessary to reduce the severity of illness, prevent development of complicated disease and extraintestinal spread, and decrease transmission. This review aims to evaluate anti-amoebic drugs for treating amoebic colitis. 

Soil-transmitted helminthiases

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) [7]. 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.[7] 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.
Open Access
Antihelminthics in helminth‐endemic areas: effects on HIV disease progression
Helminth infections, such as soil-transmitted helminths, schistosomiasis, onchocerciasis, and lymphatic filariasis, are prevalent in many countries where human immunodeficiency virus (HIV) infection is also common. There is some evidence from observational studies that HIV and helminth co-infection may be associated with higher viral load and lower CD4+ cell counts. Treatment of helminth infections with antihelminthics (deworming drugs) may have benefits for people living with HIV beyond simply clearance of worm infections. This review evaluates the effects of deworming drugs (antihelminthic therapy) on markers of HIV disease progression, anaemia, and adverse events in children and adults.
Free Access
Effect of administration of antihelminthics for soil‐transmitted helminths during pregnancy
Over 50% of the pregnant women in low- and middle-income countries suffer from iron-deficiency anaemia. Though iron-deficiency anaemia is multifactorial, hook worm infestation is a major contributory cause in women of reproductive age in endemic areas. Antihelminthics are highly efficacious in treating hook worm but evidence of their beneficial effect and safety, during pregnancy, has not been established. This review determines the effects of administration of antihelminthics for soil-transmitted helminths during the second or third trimester of pregnancy on maternal anaemia and pregnancy outcomes.
Open Access
Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection
Strongyloidiasis is a gut infection with Strongyloides stercoralis. Chronic infection usually causes a skin rash, vomiting, diarrhoea or constipation, and respiratory problems, and can be fatal in people with immune deficiency. This review assesses the effects of ivermectin versus benzimidazoles (albendazole and thiabendazole) for treating chronic strongyloides infection.


Schistosomiasis, also referred to as bilharzia, is caused by trematode worms of the genus Schistosoma. It is transmitted when larval stage parasites penetrate human skin during contact with infested freshwater. Symptoms depend upon the parasite species; most human infections are caused by Schistosoma mansoni, S. haematobium, or S. japonicum.
Open Access
Circulating antigen tests and urine reagent strips for diagnosis of active schistosomiasis in endemic areas
Point-of-care tests for diagnosing schistosomiasis include tests based on circulating antigen detection and urine reagent strip tests. With sufficient diagnostic accuracy they could replace conventional microscopy by being easier to use and providing a quicker answer. This review summarises the diagnostic accuracy of: (1) urine reagent strip tests in detecting active Schistosoma haematobium infection, with microscopy as the reference standard; and (2) circulating antigen tests for detecting active Schistosoma infection in geographical regions endemic for Schistosoma mansoni or S. haematobium, or both, with microscopy as the reference standard.
Open Access
Drugs for treating urinary schistosomiasis
Urinary schistosomiasis is caused by an intravascular infection with parasitic Schistosoma haematobium worms. The adult worms typically migrate to the bladder and excrete eggs which the infected person passes in their urine. Chronic infection can cause substantial morbidity and long-term complications as the eggs become trapped in human tissues causing inflammation and fibrosis.  This review evaluates the efficacy and safety of drugs for treating urinary schistosomiasis.

Lymphatic filariasis

Lymphatic filariasis is a parasitic infection of threadlike, filarial worms. Spread by female mosquitoes and affecting about 120 million people [8], the infection can cause severe disability due to 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 (Brugia malayi) and Indonesia (Brugia 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 review aims to assess evidence of the effects of albendazole on the disease and the parasite, and to summarise the effects of albendazole alone or in combination with antifilarial drugs for clinical treatment and community control of lymphatic filariasis.


Onchocerciasis, also known as ‘river blindness’, is caused by the parasitic worm Onchocerca volvulus. It is caused by the bite of infected blackflies of the genus Simulium. And symptoms include visual impairment, severe itching, and skin disease.
Free Access
Doxycycline plus ivermectin versus ivermectin alone for treatment of patients with onchocerciasis
Onchocerciasis is the second leading infectious cause of blindness in areas where it is endemic. The main aim of this review was to assess the effectiveness of doxycycline plus ivermectin versus ivermectin alone for prevention and treatment of onchocerciasis. The secondary aim was to assess the effectiveness of doxycycline plus ivermectin versus ivermectin alone for prevention and treatment of onchocercal ocular lesions in communities co-endemic for onchocerciasis and Loa loa (loiasis) infection.
Free Access
Ivermectin for onchocercal eye disease (river blindness)
It is believed that ivermectin (a microfilaricide) could prevent blindness due to onchocerciasis. However, when given to everyone in communities where onchocerciasis is common, the effects of ivermectin on lesions affecting the eye are uncertain and data on whether the drug prevents visual loss are unclear. The main aim of this review was to assess the effectiveness of ivermectin in preventing visual impairment and visual field loss in onchocercal eye disease. The secondary aim was to assess the effects of ivermectin on lesions affecting the eye in onchocerciasis.