SANDFLY – PAPPATACI FEVER IN BOSNIA AND HERZEGOVINA: THE NEW-OLD DISEASE
&Mirsada Hukić*, Irma Salimović-Bešić
Institute of Clinical Microbiology, University of Sarajevo Clincs Centre, Bolnička , Sarajevo, Bosnia and Herzegovina
* Corresponding author
Abstract
Sandfl y fever viruses (SFV) are endemic in the Mediterranean, Middle East, northern African and western Asian countries. Toscana virus (TOSV), serotype of Sandfl y fever Naples virus, is among of the three most prevalent viruses associated with meningitis during the warm seasons in northern Mediterranean countries. Th e historical data of the sandfl y fever (Pappataci fever) indicates its origin in Bosnia and Herzegovina at the end of th century. Th ere is a long period of time for which there are no data on re- search related to the SFV in Bosnia and Herzegovina. Th e purpose of the study was to investigate the presence of sandfl y fever in Bosnia and Herzegovina in recent years. Th e of serum samples were obtained from February until September from a group of patients with febrile illness of unknown etiology. Th e sera were tested on the presence of IgG and IgM antibodies against TOSV by specifi c serology test- recomLine Bunyavirus IgG/IgM immuno-line assay. Th e recent TOSV-infection was confi rmed in the patients in each year during the study: , (/) in ; , (/) in and , (/) in . Th e presence of specifi c antibodies to TOSV in the sera of the patients in recent years indicates re-emerging character of the disease in this region. It would be necessary to make biological, epidemiological and clinical research on the TOSV and related phleboviruses to elucidate the problem of SFV in Bosnia and Her- zegovina.
KEY WORDS: Phlebovirus, Sandfl y fever viruses, TOSV, phlebotomus fever, Pappataci fever
BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES 2009; 9 (1): 39-43 MIRSADA HUKIĆ, IRMA SALIMOVIĆBEŠIĆ: SANDFLY PAPPATACI FEVER IN BOSNIA AND HERZEGOVINA: THE NEWOLD DISEASE
Introduction of “Pappataci“ mosqitos in some military barracks in Herzegovina (). These “Pappataci“ mosqitos hit Sandfly fever viruses are classified among family Bu- only during the night. “Th e dog disease“ was appeared nyaviridae, genus Phlebovirus. They are endemic in just in places where “Pappataci“ mosqitos occurred. the Mediterranean, Middle East, northern Afri- In , Giovanni Battista Grassi (-) can and western Asian countries, where they rep- studied about “phlebotomus papatasii“ in resent a significant health problem, especially for Rome and described this type of mosqito (). non-native and non-immune visitors (). These vi- In summer , leadership of Committee constituted ruses are responsible for a human disease known as of physicians Franz, Taussig and Doerr took the mis- sandfly fever, phlebotomus fever or Pappataci fever. sion to explore the infective agent of the disease (). Although the genus Phlebovirus consists currently of Doerr found out that a virus is a causative agent and distinct virus serotypes, eight serotypes, namely Alen- the infected pappataci mosqito is vector of the dis- quer, Candiru, Chagres, sandfly fever Naples, Punta ease. Th at was assumed by Taussig. Commettee made Toro, Rift Valley fever, SFSV and sandfl y fever Toscana the issue to term the disease as “Pappataci fever“, re- virus (TOSV), have been linked to disease in humans (). spectively, in honor of Grassi “Phlebotomus fever“ (). TOSV is endemic in central Italy and described as However, at the beginning of the history of develop- the most frequent cause of aseptic meningitis in chil- ment of the disease is the name of Alois Pick, who gave dren in that region (, ). As a consequence of the life the origin of the disease in Bosnia and Herzegovina. cycle of Phlebotomus, TOSV is more frequent during During the World War II, the disease affected large summer, with a peak in August. The most common numbers of soldiers serving in the Mediterranean op- presentation is an acute febrile illness or meningitis, erations, especially USA Army personnel. Th e disease and more rarely a meningoencephalitis (-). Most was first recognized among American soldiers when of the studies on TOSV have been done in central the morbidity rate of febrile cases increased during the Italy, but the occurrence of TOSV in other countries period they spent in North Africa (end of April ). such as France, Spain, Slovenia, Greece, Cyprus, Tur- Study of the infected military personnel led to the clini- key and Egypt, has also been reported recently (). cal description, the discovery of the vector of the dis- ease (Phlebotomus papatasii) and the isolation of the History of sandfl y fever responsible viruses, namely sandfl y fever Sicilian virus Th e fi rst who described the disease was Austro-Hungar- (SFSV) and sandfly fever Naples virus (SFNV) (). ian military doctor of medicine from Trebinje (Herze- After World War II, the disease occurred in Serbia and govina), Czech Alois Pick. In , he published an ar- the first epidemic of pappataci fever in this Republic ticle entitled “Pathology and the therapy of the domestic was described by Karakašević in ().Th e epidemic endemic disease“ in “Wiener medizinischen Wochen- aff ected East Serbia, then Belgrade, where there were schrift“ (). He rejected the use of the name of the disease several thousand sick persons. In the same year, the fi rst “gastroenteritis endemica“ which was in use by many cases occurred in Banat, and in a new epidemic physicians, because of its medical nomenclature, and in- struck the southern part of that region, where over troduced a new term of the disease “the dog disease“. Th e of the inhabitants were taken ill (). Th e epidem- new term was commonly used by people and soldiers. ics remained without etiological confi rmation, and the In , Pick was intensively involved in study of “the dog presumptive diagnosis was based on the clinical pic- disease“ (), when the disease occurred around Trebinje ture, epidemiological data and entomological fi ndings. and Stolac (Herzegovina). He knew that similar disease occurred in Mostar and Ljubuški (Herzegovina), and in Th ere is a long period of time for which there are no data Korčula and Dubrovnik (Croatia), as well. Foreigners on research related to the sandfl y fever (phlebotomus fe- were more exposed to the disease than native population. ver or Pappataci fever) in Bosnia and Herzegovina. Ac- Also, other scientists were study about “the dog disease“. cording to the historical data of the phlebotomus fever Without knowledge of Pick, Gabel investigated the dis- in Bosnia and Herzegovina and emergence of Toscana ease in Mostar, Trebinje and Stolac (Herzegovina), and Virus in Europe, fi nding disease in this region is to expect. thought on “acclimatization disease“, that had never Aim of this study was to investigate the pres- been noted in Spring, Autumn and Winter time (). ence of sandfly fever in Bosnia and Herzegovi- In , Taussig performed broad clinical and epi- na (B&H) in a group of patients with febrile ill- demiological research and found out the existance ness of unknown etiology, from till .
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Material and Methods Positive IgM-finding without a positive IgG- finding was found in three samples of sera. Th e study was retrospective. Th e serum samples were They are evaluated as borderline (Figure ). collected from February until September from a group of patients with febrile illness of unknown etiology. All the patients were hospitalized in Univer- sity of Sarajevo Clinics Centre, Bosnia and Herzegovina. Samples sera were tested on the presence of IgG and IgM antibody directed against TOSV by the recomLine Bu- nyavirus IgG/IgM immuno-line assay (Mikrogen GmbH, Germany) according to the manufacturer’s instructions The test is based on specific recombinant antigens for the determination of IgG- and IgM-antibodies against Hantavirus (serotypes Hantaan, Puuma- la, Seoul and Dobrava) as well as Sandfly Fever Vi- rus (serotype Toscana) in human serum or plasma. According to the manufacturer’s instructions a positive IgM-fi nding without a positive IgG-fi nding is evaluated as borderline. A serum with a borderline or even nega- tive IgM result and positive IgG result could indicate a re- cent infection. In acute cases of the disease, IgG and IgM antibodies should be detected, confi rming the diagnosis.
Results
Anti-TOSV IgG and IgM were analyzed in human serum samples. Recent infection was found in seven patients (, ). Th e fi ndings are presented in Table , Figure and . There was not a case with IgM and IgG anti- bodies against TOSV present at the same time. recomLine Bunyavirus IgG/IgM
immuno-line assay The recent infection was conformed in the patients Year Results anti-TOSV IgG anti-TOSV IgM in each year during the study: , (/) in ; 2008. Positive 3 (10,71%) , (/) in and , (/) in (Figure ). 2 (7,14%) Negative 25 (89,29%) 26 (92.86%) Discussion Recent infection 3 (10,71%) Total samples 28 (100%) 2007. Positive 3 (9,38%) Before World War II, the papatasi fever in the former Negative 29 (90,62%) 32 (100%) Yugoslavia was known mainly in Herzegovina, Dalma- Recent infection 3 (9,38%) Total samples 32 (100%) tia, Montenegro and especially in Macedonia, where its 2006. Positive 1 (12,50%) prevalence coincided with that of Phlebotomus papatasi. 1 (12,50%) Th e fi rst cases of pappataci fever in Bosnia and Herze- Negative 7 (87,50%) 7 (87,50%) govina were detected at the end of th century (, ). Recent infection 1 (12,50%) Most of the clinical and epidemiologic studies have been Total samples 8 (100%) TOTAL CASES conducted in Bosnia and Herzegovina between and WITH RECENT 7 (10,29%) (). After that period, interest for the pappataci INFECTION fever has disappeared. Th ere is no published data about TOTAL 68 (100%) SAMPLES the TOSV infection after in the B&H, the year when the virus was originally isolated in central Italy (). TABLE 1. Prevalence of anti-TOSV antibodies detected by recomLine Our study presents the evidence of occurrence of the Bunyavirus IgG/IgM immuno-line assay (Mikrogen GmbH, Ger- TOSV infection among the selected group of patients many) in group of patients with febrile illness of unknown etiology in BiH during the years 2006-2008. with febrile illness of unknown etiology. We have found
BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES 2009; 9 (1): 41-43 MIRSADA HUKIĆ, IRMA SALIMOVIĆBEŠIĆ: SANDFLY PAPPATACI FEVER IN BOSNIA AND HERZEGOVINA: THE NEWOLD DISEASE
IgM positive results in three cases (two in , and one the Naples virus in the inhabitants of Bosnia and Her- in ). However, no positive findings in IgG were zegovina in . In subsequent work (), it has been detected for these patients. Th ese results where evalu- seen that the prevalence of the Naples virus infection ated as borderline and it was recommended to retest reached ,. Th e signifi cant importance was the fi nd- the new serum samples. We did not have the results ing of antibodies in , of children aged - years. Th e of the retested samples so we could not confi rm or re- similar results were obtained by Salja and associates in ject the diagnosis of TOSV-infection. In all other cases, Kosovo, in (). Th ese results indicated the con- IgG positive fi ndings represented the recent infection. tinual circulation of Naples virus in nature. Th e results In , our laboratory experiences showed a large of faunistic and ecological investigations of the sandfl y number of bacteriological sterile liquor samples vectors associated with this virus have been published (/; ,) of patients with CNS disease (un- (,-). Th e oldest data on the study of sandfl ies in published data). This could imply that virus was former Yugoslavia, exactly in Bosnia and Herzegovina, ethological agent of the infection in those patients. are in the works of Strobl (,), where the detection The recent infection was found in , to , of of the Phlebotomus papatasi was fi rst mentioned. Th e patients during the period of three years ( – ). virus of Naples pappataci fever was the fi rst causative Th e percentage of the positive sera in that period is less agent of the disease isolated in former Yugoslavia (). then forty years ago. In - Tesh et al. () made Finding the TOSV positive results as member of the ge- the fi rst extensive serological investigations in this fi eld, nus Phlebovirus in clinical samples after more than forty reported their fi ndings, indicating the high prevalence years (), means that the virus has still circulating in this of the antibodies to Naples and Sicilian sandfly fever region, but has not been the point of interest of the lo- viruses in population of Dalmatia, North Croatia and cal explorers. It is very important to direct the attention Kosovo. On the island of Brač, , of the population of clinicians to sandfl y fever (pappataci fever) because had antibodies for the Naples virus and , for the the disease was unrecognized in B&H in the last time. Sicilian virus; in Kosovo- , had Naples antibodies It would be necessary to make the research on and , had Sicilian. In this research on the prevalence the TOSV and related phleboviruses in its nat- of the arbovirus infection, Terzin et al. () discussed ural reservoir and in men, as well as to com- the data on the detection of residual antibodies for pare the results with data available in literature. Conclusion
Th is study confi rms that TOSV as a serotype of Sandfl y fever Naples virus circulates in Bosnia and Herzegovina for cen- turies. Th e presence of such phlebovirus in recent years indicates re-emerging character of the TOSV infection in this region. Despite increasing evidence of its major role in medicine as an emerging cause of CNS infections, TOSV remains an un- studied pathogen. Th e recent data on TOSV circulation in Mediterranean countries and so in Bosnia and Herzegovina raises concern about potential implications for blood donations, because of the asymptomatic course of illness in major- ity of cases.
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