General prevalence : 6 à 8 millions

1. IS CHAGAS’ DISEASE A REAL THREAT TO THE VIETNAM ? Jean-François PAYS - Société de Pathologie Exotique – Paris Université du Nordeste , Corrientes - Argentine

2. False emergence : no vector transmission or circulation of the parasiteRare cases of transmission by transplant or blood transfusion. Possibility of congenital transmission in infected migrant women. Chagas’disease was considered for a long time as emblematic of the Latin American subcontinent. Its globalization today is done because of the legal and illegal transcontinental migratory flows, but its vector transmission remains limited to the countries of Central and South America, mainly but non only because of the absence, except in this geographical area,..of competent vectors

3. in sufficient number, living in contact with man, feeding on his blood and reproducing in his house. These three linked conditions are essential in the epidemiology of the disease. In Vietnam, these conditions are on the way to be fulfilled. Does this mean that Chagas’disease is a threat to this country?Question which we are going to try to answer General prevalence : 6 à 8 millions to man++

4. The vectors of Trypanosoma cruzi , agent of the Chagas’disease , belong to the family of Reduviidaewhich is divided in two subfamily Reduviinae (prédators ) Triatominae( blood sucking in both sex and in all stages 1 cm Rhodnius prolixus: adulte, 5 larval stages The sub-family of Triatominae (kissing bugs) has 7 genera and more than 145 species) 95 % of them are strictly American 1/3 of it were found naturally infected by T.cruzi, all in the Americas A dozen only plays an important or very important role in the transmission of the Chagas’ disease.

5. The 5% (13) of the remaining species are asian and only one is cosmopolitan (except Europa) : Triatoma rubrofasciata ( on map ) The genus Linchosteus is Indian. Geographic distribution of Triatominae in the Old World :5 % Vietnam particulièrement concerné 6 sp 7 species ofTriatoma very close –dérivéd ?– of T.rubrofasciata) of which T bouvieri in Vietnam d’après JC Schofield from Schofield JC WWW.pathexo.fr/documents/agenda/SPE-Chagas-4.pdf Dujardin JP ,Pham Thik K, Truong Xuan L et col 2015 Act Trop 15:142-9

6. Triatoma rubrofasciata In the Americas, is a competent and active vector of T cruzi in particular in the Brazilian, partially Amazonian, state of Maranhao. He is strongly associated to the rodents, in particular to Rattus rattus , to whom it tranmits by oro-faecal way a non- pathogenic trypanosome T. conhorini As shown by its coastal location in Asia as in Africa, its dispersion seems to have been made from America (probably North America) by merchant ships infested with rats and borrowing the east road . T.rubrofasciata would be at the origin of all other species of Triatominae present in Asia (including that of the genus Linchosteus)

7. Two particularities characterize the presence of T.rubrofasciata au Vietnam: -Its invasive character: T. rubrifascita penetrate farther and farther inside lands and colonizes both rural and urban environment (21 provinces affected and all the big cities, in particular Hanoi where the bug is found up to the fifth floor of houses (Nguyen Van Chau). -Its progressive domestication and association with the man on whom it feeds more and more frequently Dujardin JP, Lam TX, Khoa PT et col 2015 Mam Inst Oswaldo Cruz 11(3) 319-323 Présence of T.rubrofasciata in Hanoi active/passive investigation 2010-12- but non exhautive Enquête active/passive non exhaustive Van Chau N. et col. http://wwwmome-clic.com/wp-content/…/Chinh_Chau_Tr_Vietnam

8. The allergic manifestations to the repeated bites by Triatominae is a known long-time phenomenon (xenodiagnostic)- The clinical manifestations after the bites of T rubrofasciata in Vietnam are often marked and vary from pruritus to anaphylactic choc including hives, local swellings which can reach the size of an pigeon egg, and fever in 5 to 25 % of the cases, This swellings must not be confused with a chagoma, classic gateway to T.cruzi ,with the Romana’sign A raising sensitization to the faeces of Triatominae is also possible, at the origin of respiratory symptoms. xenodianosis Differential diagnosis in endemic area from Truong Xun Lam Mem Inst Oswaldo Cruz 110 (3) 321 Chagoma gateway ofT cruzi

9. Thus, with T rubrofasciata, Vietnam is home to a bug which is a real nuisance and which gradually acquires all the necessary behavioral qualities to be an effective vector of Chagas’disease if it is accidently infected with T cruzi. How T. cruzi could be introduced in Vietnam? - introduction of bugs infected from Americas, stowaways of the bundles packaging, goods, containers and luggage - introduction of "healthy carriers" of T cruzi (tourists), in reality people in undetermined chronicle stage, undetectable except a systematic serology - introduction of animals infected of the same origin (dog, cat, rats, mouse, Nac: armadillos, monkey … (Some 200 animal species are reservoir in endemic area

10. Likely scenario a)Creation, at first, of an animal reservoir extremely difficult to detect, b)Then, always through T.rubrofasciata, appearance of the first human case so very difficult to detect because 1- the most of the acute stage are undiagnosed in the adult even in endemic area because the symptoms are often missing or atypical 2- the asymptomatic chronic stage during which the parasite is undetectable by techniques usually used can last several decades and even, in 2/3 of the cases, all the life of the infected man witch is in this way an excellent reservoir of T cruzi 3-the symptoms of the symptomatic chronic phase are not always charac-teristic even if some of them are very suggestive when present: mega-organs, hearth blocks, dilated cardiomegaly, aneurysm of the apex…, c)The perenniality could be insured by vectorial transmission as sporadic case, by blood transfusion and by congenital way

11. The microscopic confirmation of any positive serology requested at the slightest doubt will have to take into account the very low number of parasites which characterizes the chronic phase and must be confirmed by PCR because of the presence in Vietnam of at least 3 animal trypanosomes able infect the man. T. conorhini, parasite of rats, transmis par T rubrofasciata ( 50% infected) by oro-faecal way. No human cases reported but it is an asymptomatic parasitosis. Found also in the macaques :could it be a parasite of monkey passed to the rat? T lewisi transmitted to rodents by oro-faecal way by dropping fleas. Transient and asymptomatic infection. A dozen of human cases reported. Resistant to human serum even supplemented by apolipoproteine (APOL 1). T evansi agent of surra (buffaloes- horses) (close to nagana): 1 human case in Vietnam, confirmed, (N. Van ChauCID 2016:62) 1 human confirmed case in India fatal in a APOL 1 deficit 3 other non-confirmed human cases in India and 1 in Egypt.

12. Although not zero, the risk of the introduction of T. cruzi and Chagas’ disease in Vietnam and its sustainability by vector transmission in relation with the presence of T.rubrofasciataseems low, and even very low in the present context, limited, among others, by the following facts : 1-the persistence of the close relations of Triatoma rubrofascita with rats and rodents limits the risk that this bug becomes infected by a non infected imported non-rodents species, and also the one to create a very diversified reservoir. But an significant increase of the frequency of its blood meals taken on human (10 à 50 % in 2012 according to the type of investigation with an average of 15 %) , and an adaptation of the bug to a new situation, could be done quickly 2-the behavior of this bug which defecates long after its blood meal, as well as its poor resistance to the starvation, make of it a relatively mediocre potential vector 3- the number extremely low of the people native of Latin America living in Vietnam and thus susceptible to be carrier of the parasite helps to reduce very significantly the risk .

13. The epidemiology of every disease has its own genius. The non-importation of the yellow fever in Asia is a good example. In spite of the favorable conditions aforesaid, the accidental importation of T cruzi in Vietnam, as well as its sustainability to the animal, would not automa-tically mean the occurrence and onset of the human disease in this country,as shown, for example, by the status of T. cruzi in USA 27 US states withT riatominae (11 species) and most T cruzi but Many other factors indeed come into play in the epidemiology of the Chagas’ disease that do not fall under entomology : human, behavioral, economic, politic… only7 confirmed human cases It is nevertheless desirable that the Vietnamese practitioners remain watchful on the subject and know enough the Chagas disease as well as pitfalls of its diagnosis to be able to play effectively a sentinel's role..