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The neglected tropical diseases NTDs are the most common infections of the world's poorest people living in Africa, Asia, and the Americas . The NTDs differ significantly in their prevalence and disease burden according to their geographic and regional presence.
Here, we summarize current knowledge on the prevalence, distribution, and disease burden of the NTDs in India and South Asia, focusing on aspects particular to the region. Recently, a comprehensive review on the continuing challenge of infectious diseases in India was published . However, this review focuses exclusively on NTDs, many of which, especially the helminthiases, were not emphasized previously .
There is no single and universally accepted definition of the geographic area known as South Asia; however, most definitions include the nations of Bangladesh, India, Maldives, Nepal, and Sri Lanka. Because the prevalence and disease burden of the major NTDs in East Asia were previously reviewed and included those five countries  , we instead adopted the World Bank's use of the term South Asia , which incorporates the eight nations of Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka  ,  Figure 1.
With a few exceptions, very little data on the NTDs are available from Afghanistan, so the information provided here emphasizes the NTDs in the other seven countries. Together, the South Asian nations mentioned above represent a population of 1. Today, South Asia accounts for approximately one-quarter of the world's soil-transmitted helminth infections, one-third or more of the global deaths from rabies, and one-half or more of the global burden of lymphatic filariasis, visceral leishmaniasis, and leprosy.
The region is also experiencing an emerging problem with three major arbovirus infections, i. For several other important NTDs, such as strongyloidiasis, toxocariasis, leptospirosis, and amebiasis, there are no prevalence or disease burden estimates available. The major helminth infections in South Asia include three soil-transmitted helminth infections, i.
Ascariasis Ascaris lumbricoides infection is the most common helminth infection and NTD in the region, with more than million cases, followed by more than million cases of trichuriasis Trichuris trichiura and hookworm, respectively  , . Whereas Necator americanus accounts for most of the world's cases of human hookworm infections, in Uttar Pradesh and West Bengal States, and presumably elsewhere in India, mixed infections with both N.
In Pakistan, wastewater used in agriculture was found to be a significant risk factor for hookworm . Overall, South Asia accounts for approximately one-quarter of the world's cases soil-transmitted helminthiases, with the largest number of cases in India, followed by Bangladesh.
These numbers are based on data published in  ; more recent data from the Global Atlas of Helminth Infections  are not yet available for South Asia. The major strategy relies on once or twice yearly mass drug administration MDA using the drug mebendazole or albendazole as a single dose, with a drug delivery system relying heavily on schools and schoolteachers administering the drugs.
Among school-aged children only Bhutan has achieved this target to date, although approximately one-half of Sri Lanka now receives regular deworming in national control campaigns . However, a higher percentage of pre-school-aged children receive deworming, especially in Bangladesh, India, Nepal, and Sri Lanka, possibly because children receive single-dose albendazole as part of lymphatic filariasis LF elimination efforts that combine MDA with this drug together with diethylcarbamazine citrate DEC.
In addition, Nepal has been targeted for helminth control, together with LF and trachoma elimination efforts, through a United States—supported NTD Program  , while in Sri Lanka the overall prevalence of soil-transmitted helminth infections among school-aged children falls below the WHO-recommended level required for annual deworming . A human hookworm vaccine is also under development to prevent post-treatment re-infection .
LF is one of the most debilitating and disfiguring diseases in South Asia, where almost all of the cases are caused by Wuchereria bancrofti  , . The adult worms inhabit the lymphatics, which in late stages lead to lymphoedema and elephantiasis. The disease is poverty-related and predominantly affects poor and marginalized groups .
LF-associated disabilities and deformities result in heavy economic losses and loss of livelihood . There is also a huge socioeconomic impact  due to impaired worker productivity resulting from lymphoedema of the lower limbs and hydrocele  , . The main strategies are: 1 annual MDA with two drugs, DEC and albendazole, to the entire eligible population for 5—6 years, and 2 home-based disability alleviation and prevention  , . Today, with treatments offered to the entire endemic population of million people, MDA for LF in India is that country's largest national public health intervention .
The overall prevalence of microfilaremia for LF was cut in half between and and today the prevalence is 0. Leishmaniasis and amebiasis represent the highest burden protozoan NTDs. In South Asia, VL is caused by Leishmania donovani and transmitted to humans by the bite of an infected female sandfly, Phlebotomus argentipes. VL lowers immunity, causes persistent fever, pancytopenia, and enlargement of the spleen and liver, and leads to very high mortality in untreated cases.
Post kala-azar dermal leishmaniasis PKDL is also an important complication. In this condition, numerous parasites are lodged in the lesions in the skin, creating a chronic source for further transmission. In South Asia VL is mainly a rural disease predominantly affecting the poor, and poverty is a key determinant of this disease  , . Among the risk factors that promote survival of the insect vector and foster disease transmission are mud walls, dampness in houses, and peridomestic vegetation .
It has also been noted that women often delay seeking VL treatments and are more likely to die from their infection . Even though VL in South Asia is anthroponotic there is no significant animal reservoir , in some studies the presence of cattle is associated with an increased risk of acquiring the infection  , . VL cases tend to cluster at the household level and entire villages can become infected during a VL epidemic over a short period which is then often followed by an outbreak of PKDL cases .
Like many NTDs, VL may actually promote poverty because of its impact on children and worker productivity . In addition, the families of VL patients must often use a significant percentage of their earnings or savings for often expensive treatments.
The high cost is a particular problem in the impoverished state of Bihar where antimonial drug resistance is high and the alternative treatments, especially liposomal amphotericin B, are often prohibitively expensive  , . The elimination goal received a boost in when the ministers of health of Bangladesh, India, and Nepal met in Kathmandu, Nepal, under the auspices of the WHO, endorsed a joint action strategy for this goal, which includes an administrative commitment to eliminate VL by .
Following the ministerial meeting, a draft regional strategic plan was developed and endorsed by the three countries during an inter-country meeting held in Varanasi, India, in November The major elements of the strategy include: 1 early diagnosis wherever possible, with the rapid diagnostic test rk and prompt treatment with the oral drug miltefosine, injectable paromomycin, or liposomal amphotericin B  ,  ; 2 integrated vector management, which includes bed nets and indoor residual spraying with DDT and other agents  ,  ; 3 effective disease surveillance; 4 social mobilization and partnerships; and 5 clinical and operational research  , .
Several candidate vaccines to prevent VL are also under development . In addition to the problem of VL, Afghanistan has experienced a re-emergence of disfiguring cutaneous leishmaniasis CL , especially in Kabul .
Conflict and its association with a weakened health care infrastructure combined with environmental degradation are key factors believed to be responsible for this resurgence . Amebiasis is another important protozoan infection, especially in India and Bangladesh, although there are minimal surveillance data available and no known disease burden information.
Among the difficulties in elucidating the extent of this infection is the absence of widespread testing to differentiate amebiasis caused by pathogenic Entamoeba histolytica versus the non-pathogenic Entamoeba dispar . The major neglected bacterial infections in South Asia include leprosy, trachoma, and leptospirosis. Caused by Mycobacterium leprae , leprosy is one of the oldest diseases known to humankind.
The disease primarily affects skin and peripheral nerves, which can lead to crippling deformities of the hands, feet, and face if left undiagnosed or untreated. The disease disproportionately affects the poor and other vulnerable and marginalized population groups; its victims are often exposed to stigma, prejudice, discrimination, and ostracism.
By the end of , of the countries Brazil being the only exception have achieved the leprosy elimination goal at the national level and several of them have also achieved the goal at the sub-national level.
The Global Leprosy Programme is thus one of the outstanding success stories in public health. Currently, of the world's , registered cases of leprosy, more than one-half still occur in South Asia . Nepal was the last country in the region to achieve the leprosy elimination goal in Worldwide, trachoma is a leading cause of visual impairment and blindness.
According to the WHO's world trachoma atlas using data from , approximately 1 million cases of trachoma occur in India, particularly in Rajasthan  , and ,—, cases in Afghanistan, Nepal, and Pakistan . However, other sources indicate that India may account for a much larger contribution to the global trachoma disease burden  , .
Although leptospirosis is believed to be an important NTD in South Asia, there is a paucity of prevalence and disease burden information. However, because of its association with flooding, leptospirosis is believed to be an important cause of acute febrile illness in children and aseptic meningitis, especially in the monsoon and immediate post-monsoon seasons .
The disease is endemic in the Indian states of Kerala where the seroprevalence is especially high among high-risk groups such as sewage workers, hospital sanitary workers, and fisherman , Tamil Nadu, and the Adamans, and outbreaks are common in the slums of Mumbai .
The major neglected viral infections in India and South Asia include the two major arboviral infections, dengue and Japanese encephalitis, and rabies. However, at least a dozen other epidemics of a dengue-like illness were recorded throughout the 19th and 20th centuries . Dengue hemorrhagic fever was first reported from India only in , with a large outbreak occurring in Delhi in  , .
Although initially a largely urban disease, dengue has now spread to rural areas  —  , with dengue cases occurring throughout the year . In Bhutan and Nepal, dengue was first reported in  , . Dengue continues to be reported in all countries of South Asia and sustained vector control efforts need to be initiated.
JE is believed to have been introduced to South Asia from East Asia within the last half of the 20th century . As a result of its recent emergence in the region, JE affects both children and adults in northern India, Nepal, and Sri Lanka, whereas it is predominantly a pediatric disease in the Asia-Pacific region . Large epidemics in northern India and Nepal occur primarily during the summer months . Although JE can be a highly fatal disease, most individuals are asymptomatic.
Due to the absence of vaccination programs and possibly other interventions, the incidence of JE in Bangladesh, India, and possibly Pakistan was noted previously to be on the rise, whereas it had decreased in Nepal and Sri Lanka, where both surveillance and vaccination programs are in place .
Two key factors responsible for JE emergence in South Asia include population growth and irrigated rice farming, which creates suitable breeding sites for mosquito vectors . Climate change may also represent an important factor. In addition to the vaccination programs in Nepal and Sri Lanka, the Indian Ministry of Health has recently developed plans for surveillance and national vaccination of children; immunization programs have begun in both Tamil Nadu and Uttar Pradesh .
More than 9 million children were vaccinated in India in , and since then vaccination programs have been introduced into all 62 endemic districts .
Chikungunya was first identified in Tanzania in the early s and has caused periodic outbreaks in Asia and Africa since the s. It is rarely fatal. Significant pain occurs in the joints and the pain can persist for several weeks. Chikungunya shares some clinical signs with dengue and can be misdiagnosed in areas where dengue is common.
Between and , a number of countries reported Chikungunya outbreaks. In an outbreak in India in , 1. Rabies is an important neglected zoonotic disease in South Asia. Almost all of these deaths are preventable through prompt medical attention comprised of wound cleaning and care and post-exposure prophylaxis with rabies vaccine.
It is estimated that the canine population of India is as high as 25 million  , which makes a national program of canine mass vaccination difficult even though it is considered one of the most cost-effective ways to reduce human rabies deaths .
In , an Indian pilot project to prevent human rabies deaths was launched by the National Centre for Disease Control in five Indian cities. The project includes programs to increase awareness by the public and health care professionals about the importance of immediate medical attention to animal bites and scratches . In addition, Sri Lanka has made great strides in eliminating dog rabies, while Nepal is producing its own rabies vaccines for humans and dogs .
Throughout the affected enzootic countries it was recommended that comprehensive national rabies control programs should be established . Together, the NTDs result in an estimated 5.
They include activities of the Global Programme to Eliminate LF, which is conducting national programs of MDA, together with an international VL elimination effort emphasizing the large number of cases occurring in the border areas of Bangladesh, India, and Nepal, and national programs of MDT for leprosy.
Although JE has recently emerged in South Asia, it may also be controlled or eliminated through national programs of comprehensive vaccination.
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