. there have been significant achievements regarding to the millennium development goals ( mdgs ) as a global development target .
the indicators showed reflection of these achievements , such as decreasing global poverty rate , increasing the number of children going to school , decreasing child death rate , increasing access to clean water , and also increasing malaria , hiv / aids , and tuberculosis control investment .
mdgs were evaluated in the year 2015 , and there will be remaining new challenges to sustain the achievement at post-2015 era .
numerous important issues have been raised by united nation ( un ) , which are poverty and hunger elimination , improving health and education , sustainable cities , combating climate changes , and also ocean and forest conservation . in mdgs , hiv / aids , malaria , and major diseases are clearly mentioned as global development goals . in this case , there will be plenty of diseases that are not a major concern of the world .
questions were raised concerning neglected tropical disease ( ntd ) which is definitely out of the highlight . will these diseases be included in the ambitious post - mdgs sustainable development ? the new sustainable development goals ( sdgs ) , known also as the global goals , had been established after world leaders gathered on 25 september 2015 , at the united nations in new york to adopt the 2030 agenda for sustainable development and the broader and further agenda than the mdgs .
mdg explicitly stated that hiv / aids , malaria , and tuberculosis will be efficiently controlled at the end of the year 2015 .
the big three are the diseases that attract priority from sponsors , researchers , and policy makers [ 2 , 3 ] .
this situation is not the same as ntd , which has not gained any priority from them and even worsened .
the term of neglected in ntd referred to the fact that these tropical diseases are not being considered as important diseases .
ntd result in long life 's deformities and handicaps , decrease productivity and economical status , and also end up many social consequences and stigmatization . though ntd is commonly found in tropical countries , it is not identical with tropical diseases .
poverty as one of ntd determinants frequently occurs in rural area , slums , and marginalized populations living nearby the equator .
ntd in this area are closely associated with poverty and limited resources , such as clean drinking water access , poor sanitation , and healthy housing .
ntd may decrease child health , increase the health expenses and risk of ineffective treatment , decrease productivity , and result in education default .
their potential to spread in developed countries is low , because ntd are closely related with local vector and intermediate host distribution which are specifically associated with geographic region .
the technology and resource to control , prevent , and eliminate ntd are available , but not for the developing countries . who has included 17 diseases caused by bacteria , virus , and protozoa into ntd ( figure 1 ) .
helminths caused diseases that dominated ntd : taeniasis , dracunculiasis , echinococcosis , trematodiasis , filariasis , onchocerciasis , schistosomiasis , and soil - transmitted helminthiasis .
the ministry of health of indonesia reported only five ntd that can be found in indonesia , that is , leprosy , filariasis , schistosomiasis , soil - transmitted helminth , and yaws .
however , this review describes more than those five diseases and aims to address the magnitude of the problem of ntd in indonesia .
leprosy is an infectious disease is caused by mycobacterium leprae , a road shaped bacteria classified in the same genus as mycobacterium tuberculosis
leprosy may be complicated with deformity and handicap , which may decrease the ability of the patient to work in daily life .
leprosy was a serious problem in indonesia at 1980 , with 126,221 cases in 1985 .
it was noted that the significant improvement in leprosy control was because of massive promotion of leprosy prevention and multidrug therapy ( mdt ) intervention in more than 5,600 primary health centers in indonesia .
however , the new leprosy case finding in 2000 was not significantly different with year 2013 ( table 1 ) .
fourteen provinces and 160 districts , which mostly are located in java island , reported prevalence of > 1 per 10,000 population in 2009 .
leprosy epidemical indicators were significant , such as deformity grade 2 10.5% , leprosy cases in children 12.01% , and 82.43% multibacillary ( mb ) cases [ 10 , 1315 ] .
the problems of leprosy in indonesia are summarized as follows : early detection.development of more effective treatment.development of more effective vaccine.understanding immunopathogenesis of peripheral nerve damage.management of chronic erythema nodosum leprosum ( enl).deformity and stigmatization.deformity and stigmatization are serious problems among leprosy patients in indonesia .
survey conducted in subang district ( west java ) ; gresik and malang district ( east java ) ; bone and gowa district ( south sulawesi ) showed that deformity in leprosy patients occurred in 76.7% of patients .
almost 60% respondents were experienced handicaps during their life , including participating to social activity .
mdt has significant impact to decrease leprosy prevalence globally . however , there are various substantial operational and technical problems among countries and territory .
resistance of m. leprae is a serious problem because of limited effective antimicrobes for leprosy .
resistance against dapsone , that was applied as monotherapy , was initially reported in 1964 at malaysia . since then , resistance to dapsone and other drugs was reported .
theoretically , combination of more than two drugs with different action mechanism will reduce the probability of resistant in mycobacteria .
national surveillance of m. leprae resistance against mdt should be established to provide accurate data .
sporadic and partial reports were not sufficient to measure the problems and establish the programs to reduce the prevalence and spread of resistance against mdt .
phenotypic testing is the basic method for susceptibility testing of antimicrobial agents . even in the new proof of concept which combines the classical growth - based phenotypic test and dna based approach , pure culture of bacteria
efforts were documented to culture m. leprae in artificial media and animal models [ 24 , 25 ] .
mutations in the folp1 , rpob , and gyra genes are responsible for resistance to dapsone , rifampicin , and ofloxacin , respectively . to test the susceptibility of m. leprae against particular antibiotics ,
screening in north maluku and north sulawesi showed that resistance to dapsone occurs as 0.8% in new cases and 10% in relapse cases , while rifampicin occurs with 3.3% in new cases and 20% in relapse cases .
there is higher prevalence of dapsone and rifampicin resistance among relapse cases comparing with new cases .
it was noted that the incidence of resistance against dapsone and rifampicin in indonesia almost did not change between the time monotherapy was introduced and after mdt was recommended by who [ 29 , 30 ] .
yaws is a treponema pallidum subspecies pertenue infection , which may develop as chronic and recurrent disease .
yaws is nonsexually transmitted treponemal infection , which is latent and asymptomatic for years with positive serology result .
small portion ( 10% ) of the patients will undergo bone destruction leading to deformities .
diagnosis of yaws is commonly based on the clinical findings and serology [ 31 , 32 ] .
confirmatory diagnosis of yaws is using serological test , which includes nontreponemal agglutination tests , such as rapid plasma reagin ( rpr ) and venereal disease research laboratory ( vdrl ) test , and also treponemal tests such as treponema pallidum hemagglutination assay ( tpha ) , treponema pallidum particle agglutination tppa , and fluorescent treponemal antibody - absorption ( fta - abs ) .
the accuracy of yaws serological test is hampered in the area which syphilis , caused by t. pallidum subspecies pallidum , is endemically circulated .
yaws was reported in 68 ( 14% ) of 497 districts in indonesia , mostly in the eastern part of indonesia .
east nusa tenggara province reported 2,800 cases in 2012 , which is scattered at 566 small islands in this region .
however , it gradually decreases to 5,319 cases in 2011 and 3,476 in 2012 [ 10 , 34 ] .
there are several obstacles to eradicate yaws in indonesia : geographically the yaws patients are in a remote area including rural and small islands which are not easy to handle , difficulty to give benzathine penicillin for children , and also local political condition that is somehow counterproductive to the programs . who planned to eradicate yaws globally in 2020 with adoption of morges strategies .
this program intends to introduce a mass treatment in the endemic regions by using azithromycin .
however , benzathine penicillin can be used as back up in case of azithromycin is not indicated , treatment failure , or in places where azithromycin is not available .
this treatment followed an active survey every six months to detect and treat the remaining cases [ 32 , 34 ] .
the ministry of health launched yaws eradication program , aimed to eradicate yaws in 2013 , one year later than who target .
there were several approaches conducted , such as active screening new cases and contacts , empowering community , improving the capacity of health worker to diagnose and manage yaws , and intersectoral collaboration approaches .
access to health service is limited in the yaws endemic area , which obstacle the passive screening program .
reported a survey among health workers in primary health center , elementary school teachers , and parents in muna , southeast sulawesi .
they were asked about yaws to measure their knowledge about sign and symptoms , causative agent , and therapy for yaws .
another report from southwest sumba showed clean water and healthy behavior is the risk factor for yaws .
these reports showed that comprehensive intervention is needed to boost the community participation for yaws eradication .
reporting system for yaws incidence is very important to support the best intervention for yaws eradication .
learning the fact that their knowledge about yaws is remarkably low , it may diminish the validity of yaws reporting system .
insufficiency of this sector may result in delay of yaws eradication and increasing yaws contact population .
yaws eradication problem in indonesia is summarized as follows : early detection by health workers.geographical problem of endemic area.surveillances and reporting system.inadequate confirmatory laboratory test .
dengue virus consists of four serotypes : denv1 , denv2 , denv3 , and denv4 .
these viruses are responsible for infectious diseases with width spectrum of clinical manifestation : dengue fever ( df ) , dengue hemorrhagic fever ( dhf ) , and dengue shock syndrome ( dss ) [ 38 , 39 ] .
dengue virus infection is an arbovirus disease , which in indonesia is primarily transmitted by aedes aegypti and aedes albopictus .
the incidence of dhf significantly increased since reported initially in 1968 ( 0.05/100.000 ) to 3540/100,000 in 2013 . however , in 2010 , there was an extreme surge of dhf incidence to 86/100,000 .
the significant increasing of dhf incidence was parallel with decreasing of case fatality rate ( cfr ) , which is 41% in 1968 to 0.73% in 2013 .
however , it was noticed that from 1999 there was a trend of shifting to adults .
dhf incidence described here is believed not to be able to draw a clear picture of all denv infections .
. however , the proportion of those three clinical manifestations still becomes an enigma , although the awareness to the diseases , surveillance programs , diagnostic tools , and management of denv infection in indonesia have been significantly improved .
it has been realized that controlling adult mosquitoes is prone to fail reducing denv transmission .
the vector control approach should aim to interrupt the transmission cycle at an early phase through immature mosquito control , which is including larvae and pupae stages .
immature mosquitoes control is believed to be more effective . the vector control approach is still considered effective while vaccine and prophylaxis remedies continuously develop .
it seems that the socioecological approach is the best candidate to be implemented in an endemic country , such as indonesia .
community and intersectoral approach are significantly important fundamentals of integrated public health strategies for dengue vector control [ 47 , 48 ] .
as dengue infection has wide spectrum of clinical manifestation , the clinical diagnosis is confusing .
there are guidelines issued by who to respond to the need of applicable tool for clinician : who classification system   and dengue and control study ( denco ) revised clinical management .
the study concerning the two guidelines showed that in surabaya , indonesia , the denco revised clinical management guideline superior in detection of severe dengue cases .
however , in a study in semarang , indonesia , the denco guideline has failed to show its superiority .
it is true that the denco guideline needs to be adjusted in terms of geographic and age - related variations issues .
there are many factors that may be related with clinical manifestation of dengue virus infection , including human genetics involvement which is still controversially related with population , race , and geography [ 54 , 55 ] .
several methods are available for laboratory test confirmation of denv infection : virus isolation , genome detection , antigen detection , and antibody detection .
the first three methods are direct detection methods which were considered as more specific and able to confirm earlier onset of denv infection .
the antibody detection is widely used in the field because they are easy to perform and less expensive , though it is not as powerful as direct detection especially in secondary infection [ 50 , 56 ] .
rabies is an acute , progressive , incurable viral encephalitis disease that is transmitted from animal , mainly dogs , to human .
it is caused by rabies virus ( rabv ) , a member of the family rhabdoviridae , genus lyssavirus .
the highest incidence is concentrated in asia and africa . despite the fact that rabies is 100% vaccine - preventable infectious disease , it potentially threatens over 3 billion people in the world .
however , poor surveillance , underreporting , frequent misdiagnosis , and poor coordination among sectors may lead to underestimation of the burden of the disease .
ten countries of asean have been declared rabies - free asean by 2020 in the occasion of the thirty - fourth meeting of the asean ministers on agriculture and forestry ( 34th amaf ) , on september 2012 .
rabies was reported in 24 provinces out of 34 provinces in indonesia . reported human rabies in indonesia is small ( 206 cases in 2010 and significantly decreased to 119 cases in 2013 ) compared to thousands of cases reported in other countries such as india , china , and other asian countries . to control rabies transmission , indonesian
government uses one health approach which facilitates the multidisciplinary participation in management of zoonosis diseases .
however , kalimantan and sulawesi , other islands of indonesia , are the most plausible hypothetical origin of the bali rabv strains .
totally there were 133 reported human deaths because of rabies in bali from 2008 to september 2011 .
this significantly decrease of rabid human death within 3 years is a good model of rabies control for other regions or countries .
it was proposed that this success is mainly because of mass vaccination program for dogs , which is the primary ( 98% ) vector of rabies in bali . however , the number of reported humans bitten by dogs remained over 4,000 per month .
the preparedness to human rabies should be maintained , as the threat of human rabies escalation is still high .
lymphatic filariasis ( lf ) is caused by worms inhabiting the lymphatics [ 6365 ] .
approximately 65% of total cases are found in the southeast asian region [ 6668 ] .
lf cases were found in all provinces of indonesia . in 2009 , there were 11.914 lf cases reported . the number of total cases was steadily reported until 2013 . there were 11.912 cases registered in 2013 .
lf prevalence in indonesia varied from 0.5 to 27.6% , in which the highest rates were found in maluku , papua , west papua , east nusa tenggara , and north maluku provinces .
three lymphatic parasites are prevalently circulating in indonesia : wuchereria bancrofti , brugia malayi , and brugia timori [ 69 , 70 ] , which are transmitted by mosquitoes of five genera 
the site of adult - worm parasitism is within the lymphatic vessels , most commonly involving the extremities and male genitals [ 64 , 65 , 70 ] .
the disease predominantly afflicts poor people in both urban and rural areas with limited resources condition , where mosquitoes as a vector might be found in high density [ 64 , 68 ] . who launched global program to eliminate lymphatic filariasis ( gpelf ) , which relies on mass drug administration ( mda ) approach [ 68 , 71 ] .
the main goal of the program is to hamper transmission of disease between mosquitoes and human beings , mainly through mass drug distribution of diethylcarbamazine ( 6  mg / kg ) or ivermectin ( 150200  g / kg ) combined with albendazole ( 400  mg ) [ 68 , 71 ] .
it is recommended that all people at risk are involved in this program , since patients with asymptomatic infection may have abnormal lymphatics , and that early treatment may prevent subsequent lymphatic damage [ 66 , 69 ] .
the efficacy of six annual rounds of mda was studied in alor island , eastern part of indonesia .
microfilaria rates of b. timori decreased significantly after mda intervention , from 26% to 0.17% .
the prevalence of filarial - specific igg4 antibodies was significantly decreased from 80% to 6% .
the lf national plan has implemented mda campaigns in 2002 . however , due to financial and human resource constraints , districts often provide only partial coverage of the at - risk population within the district . in 2009 ,
the challenge of mda implementation in indonesia is not the efficacy of the drugs which were given to the community .
it seems that the infrastructure is the key of the implementation , which includes the availability of transportation and physical access to the target population , reliable data bases , and competence health workers .
the other challenge was to gain the trust from the community member to boost the compliance of drug administration .
currently , mda has been scaled up in a geographically scattered way to address high prevalence areas and political needs .
medical professionals , donors , universities , and ngos have played a critical role in finding new cases , assessing disease burden and supporting trainings and mda campaigns .
prevention of lf depends on mosquito vectors control , which has had limited success because development of mosquitoes resistance against insecticides .
urbanization of vast areas of tropical asia , including indonesia , has resulted in a concomitant rise in the prevalence of both w. bancrofti and b. malayi varieties of filariasis , carried by mosquitoes that breed in nonsylvatic habitats [ 68 , 73 ] .
schistosomiasis is a chronic water - borne infection caused by trematodes schistosoma , mainly found in developing countries in africa , south america , the caribbean , the middle east , and asia [ 69 , 74 , 75 ] . in indonesia
it is found in three isolated areas of central sulawesi province , namely , lindu , napu , and bada valleys . except for schistosoma haematobium that is responsible for urinary tract disease , the human schistosomes primarily affect the intestine and liver .
clinical manifestations of the disease are recognized as fever with dysenteric symptoms and loss of appetite , as well as physical growth and cognitive delay in children [ 69 , 77 , 78 ] .
disease prevalence fluctuated between 0.3% and 4.8% in napu valley and between 0.8% and 3.6% in lindu valley .
however , the prevalence of schistosomiasis in both areas tended to increase during the 20082011 period . the parasite transmission cycle involved domestic and wild animals as reservoir [ 76 , 79 ] . in 2012 , who approved the goal of eliminating schistosomiasis in endemic countries .
it focused on improving sanitary conditions and large - scale distribution of the antiparasitic drug , praziquantel to high - risk target groups , such as school - age children , child bearing age women , and individuals involved in frequent contact with contaminated fresh water .
praziquantel is well - tolerated , associated with few side effects , and has a very high therapeutic index .
moreover , a single dose praziquantel administration is usually sufficient to kill all adult worms [ 69 , 78 ] .
schistosomiasis control in indonesia has faced many difficulties even though the endemic areas are very limited [ 79 , 81 ] .
the core strategy of mda should be coupled with education to the local community , rat and snail surveillance , and support to the environmental management programs including introduction of latrines and suitable water sources . in the future
, there should be emphasis to understand the social dynamics and social change related to schistosomiasis , which may provide more information about concrete issues to control transmission of schistosomiasis .
lack of intersectoral coordination and collaboration may have occurred , possibly leading to increase transmission and reinfection rates , and be prone to control failure .
soil - transmitted helminthiasis ( sth ) is an infection with one or more intestinal parasitic worms : roundworms ( ascaris lumbricoides ) , whipworms ( trichuris trichiura ) , or hookworms ( necator americanus and ancylostoma duodenale )
. the tropical climate of indonesia is highly favourable to support the circulation of soil - transmitted helminths in the country .
there are sporadic reports regarding the prevalence of the sth which come from scattered part of the country .
the prevalence of sth was reported ranging from 40 to 70% in 80s to 90s .
however , the estimated prevalence of sth was decreased in 2005 : ascaris ( 15.2% ) , trichuris ( 12.9% ) , and hookworms ( 8.4% ) .
the survey conducted by ministry of health in elementary schools located in 33 provinces of indonesia showed prevalence of sth was 31.8% .
india ( 64% ) and indonesia ( 16% ) together are contributing 80% of the regional 's burden .
drugs used for deworming , albendazole , and mebendazole are effective and inexpensive to control sth transmission and reinfection .
the mda programme for elimination of lf which is implemented by using combination of albendazole with ivermectin or diethylcarbamazine seems to have synergistic effect to decrease the prevalence of sth .
the program targeted preschool and elementary school age . however , until this moment the country still struggles to combat sth . in conclusion , there were efforts and programs concerning ntd that were planed and implemented in indonesia .
many factors may contribute to the rendering of ntd elimination in indonesia , such as high population , wide range geographic of the archipelago , and limited resources . by the end of 2015 ntd
 the world will enter the postmillennium development goals 2015 era . 
 the achievements of the millennium development goals ( mdgs ) as a global development target need to be evaluated . 
 a sustainable new reasonable target is important for neglected tropical diseases ( ntd ) elimination in indonesia . 
 this review describes the ntd situation in indonesia and highlights problems beneath the ntd transmission . 
 multidisciplinary approach is a promising strategy to help the marginalized people . 
1. Introduction
2. Leprosy
3. Yaws
4. Dengue
5. Rabies
6. Lymphatic Filariasis
7. Schistosomiasis
8. Soil-Transmitted Helminths