Global surveillance of rickettsial diseases: memorandum from a WHO meeting.

Memoranda I Memorandums Global surveillance of rickettsial diseases: Memorandum from a WHO meeting* Rickettsial diseases are widely distributed throughout the world and are particularly prevalent in developing countries. An indirect immunofluorescence antibody test and standard protocol for its use have been developed and distributed to laboratories in 37 countries. This Memorandum summarizes the results obtained as well as the conclusions and recommendations made by participants at a WHO meeting on the Global Surveillance of Rickettsial Diseases, held in Oslo on 10 September 1991. Introduction The rickettsial diseases of man are widely, though variably distributed throughout the world. Such diseases include the typhus fevers, spotted fevers (tick typhus), scrub typhus, acute and chronic Q fever, rochalimaeal infections, and ehrlichiosis. Available evidence strongly suggests that these serious and incapacitating diseases constitute a very significant, but often unrecognized, fraction of the acute febrile disease burden in many populations, especially in developing countries. Simple but effec- tive treatments for these diseases are nevertheless available that reduce mortality to very low levels and greatly attenuate morbidity, enabling patients to return quickly to an active life. Such reductions in morbidity and mortality diminish the unnecessary drain on valuable medical resources; preventive/ control measures are also available for some of these diseases. Improved global surveillance of rickettsial diseases is urgently required to assess their preva- lence, to support the diagnosis and specific treatment of patients, to permit the development and im- plementation of strategies for their prevention and * This Memorandum is based on the report of a WHO meeting that was held in Oslo on 10 September 1991. The participants at the meeting were Dr J. Kazar, Bratislava, Slovak Republic; Dr J.G. Olson (Rapporteuw, Atlanta, GA, USA; Dr D. Raoult, Marseilles, France; Dr R. Regnery, Atlanta, GA, USA; Dr F. Segura-Porta, Sabadell, Spain; Dr I. Tarassevich, Moscow, Russian Federation; Dr M. Thibon, Paris, France. WHO Secretariat Dr Y. Pervikov, Division of Communicable Diseases. Requests for reprints of this article should be addressed to Microbiology and Immunology Support Services, Division of Communicable Diseases, World Health Organization, 1211 Geneva 27, Switzerland. A French translation of this article will appear in a later issue of the Bulletin. Reprint No. 5385 control, and to provide a sound and credible database to justify requests to funding agencies for support of such strategies. In 1987, at the WHO Consultation on Labora- tory Diagnosis of Rickettsial Diseases, in Palermo, the Directors of the WHO Collaborating Centres for Rickettsial Reference and Research, and other inter- ested participants, developed a strategy for the global surveillance of rickettsial diseases.a The immediate objective was to obtain reliable data on the global prevalence and distribution of these diseases and there- by reduce the associated mortality and morbidity. Additional objectives were to identify and character- ize strains of pathogenic rickettsiae from various parts of the world, and to transfer existing diagnostic technology to laboratories in developing countries. A diagnostic kit was developed, and the Collaborating Centres produced reagents and distributed materials for serological testing of patient's sera. The indirect fluorescence antibody technique (IFA), which has been extensively field tested, was selected as the preferred diagnostic procedure, because of its sensi- tivity, specificity, cost, and suitability for use in developing countries. A standard protocol for the procedure was provided. The following were sent to laboratories that requested them: partially purified suspensions of Rickettsia conorii and R. prowazekii antigen reagents; known positive and negative control sera; fluorescein-labelled antiglobulin for use in the IFA test; and teflon-coated slides. "Hands-on" workshops were also held in Bangladesh, Brazil, India, Nepal and Thailand to familiarize local labora- tories with the reagents and their use. a See: Laboratory diagnosis of rickettsial diseases. Bulletin of the World Health Organization, 66: 403-404 (1988). Bulletin of the World Health Organization, 71 (3/4): 293-296 (1993) © World Health Organization 1993 293 Memorandum Present study Laboratories in 37 countries agreed to participate in the surveillance by testing paired sera from patients with pyrexia of unknown origin. These laboratories were also asked to prepare line listings of the name, age and sex of patients, the date of onset of illness, date when serum specimens were collected, and the likely locations of exposure to rickettsial vectors. Titres .64 were considered positive. WHO has received data from some of the participating labora- tories, as outlined below (see also Table 1). Results Region of the Americas In Brazil, the Funda,cao Ezequiel Dias, Belo Hori- zonte, reported evidence of spotted-fever-group infec- tions among 13 (13.9%) of the 93 patients in their test population, mainly from Minas Gerais State; in contrast, the Instituto Adolfo Lutz, Sao Paolo, found no evidence of rickettsial antibodies in the 82 speci- mens from their test population. The five samples from Lima, Peru, also contained no antibodies to rickettsial organisms. However, in El Salvador, 8 (20%) of 40 samples were positive for typhus-group rickettsiae and 13 (32.5%) of 40 samples were posi- tive for spotted-fever-group rickettsiae. South-East Asia Region India, Mongolia, Nepal, and Thailand reported sero- logical evidence of typhus and/or spotted-fever- group infections. Several provinces in Mongolia reported evidence of rickettsial infections, with 48 (3.9%) of 1229 specimens containing significant antibody titres to spotted-fever-group rickettsiae and 117 (9.5%) of 1229 specimens containing significant levels of antibodies to Q fever. In India, the National Institute of Communicable Diseases, Delhi, detected antibodies to typhus-group rickettsiae in 7 (7.6%) of 92 specimens and to spotted-fever-group rickettsiae in 4 (4.3%) of 92 specimens ; the National Institute of Virology, Pune, reported that 2 (16.6%) of 12 spe- cimens had significant antibody levels to spotted- fever-group rickettsiae. In Nepal, 4 (21%) of 19 specimens showed evidence of infection with spotted- fever-group rickettsiae and 1 (5.3%) of 19 showed evidence of infection with scrub typhus rickettsiae. In Thailand, the Health Sciences Research Institute, Nonthaburi, found 25 (25%) of 100 specimens posi- tive for spotted-fever-group rickettsiae, 23 (23%) of 100 specimens positive for typhus-group rickettsiae, and 7 (7%) of 100 positive for antibodies to scrub typhus rickettsiae. Western Pacific Region In China eight patients from Shandong Province had significant titres to scrub typhus rickettsiae, as did nine patients from Jinan city. African Region The National Research Institute of Health, Addis Ababa, Ethiopia, reported that 31 (16.8%) of 184 persons had diagnostic levels of antibody to typhus- group rickettsiae. In C8te d'Ivoire, the Laboratoire de Bacteriologie-Virologie, Abidjan, observed that 16 (17%) of 94 individuals were seropositive to spotted-fever-group rickettsiae and 1 (1%) had a sig- nificant titre to typhus-group rickettsiae. In Guinea- Bissau 3 (7.5%) of 40 samples had antibody to typhus and 8 (20%) of 40 samples had antibodies to spotted-fever-group rickettsiae. Of 40 samples from Cape Verde, 3 (7.5%) were positive for antibodies to Table 1: Results of the serosurveys for rickettsial anti- bodies in persons with undiagnosed febrile illnesses No. of No. positive: specimens Scrub Region tested Typhus SFGa typhus Western Pacific China - - - 17 South-East Asia India 104 7 (7.6) 6 (5.7) - Mongolia 1229 - 48 (3.9) - Nepal 19 - 4 (21.1) 1 (5.3) Thailand 100 23 (23.0) 25 (25.0) 7 (7.0) Americas Brazil 93 0 13 (13.9) - Minas Gerais State Sao Paulo 82 0 0 - El Salvador 40 8 (20.0) 13 (32.5) - Peru 5 0 0 - Eastern Mediterranean Iran 40 6 (15.0) 11 (27.5) - Pakistan 100 18 (18.0) 13 (13.0) - Syrian Arab Republic 11 0 0 - Tunisia 69 12 (17.4) 27 (39.1) - Africa Cape Verde 40 3 (7.5) 4 (10.0) - Cote d'lvoire 94 1 (1.1) 16 (17.0) - Ethiopia 184 31 (16.8) - - Guinea-Bissau 40 3 (7.5) 8 (20.0) - a SFG = spotted-fever group. b Figures in parentheses are percentages. WHO Bulletin OMS. Vol 71 1993294 Global surveillance of rickettsial diseases typhus and 4 (10.0%) were positive for antibodies to spotted-fever-group rickettsiae. Eastern Mediterranean Region The National Hospital, Lattakia, Syrian Arab Repub- lic, tested sera from 11 persons and found no antibo- dies to spotted-fever- or typhus-group rickettsiae. However, evidence of rickettsial diseases was docu- mented in Tunisia and Pakistan. In Tunisia, the Laboratoire Regional de la Sante Publique de Sousse found that 12 (17.4%) of 69 people tested had diag- nostic titres to typhus-group rickettsiae and 27 (39.1%) had titres to spotted-fever-group rickettsiae. Results from the Khyber Medical College in the Peshawar region of Pakistan revealed that 18 (18%) of 100 persons had significant titres to typhus-group rickettsiae and 13 (13%) had significant titres to spotted-fever-group rickettsiae. Of 40 samples from Iran, 6 (15.0%) were positive for typhus-group rick- ettsiae and 11 (27.5%) were positive for spotted- fever-group rickettsiae. Conclusions and recommendations Unfortunately, limited demographic data were supplied by the participating laboratories. Little new information was obtained about the geographical distribution of rickettsiae, since rickettsial diseases were known to be endemic in the reporting countries. However, the documentation of spotted-fever- and typhus-group infections in Cote d'Ivoire is signifi- cant because it confirms previous findings. An iso- late from a patient with Sao Paulo fever was made at the Instituto Adolpho Lutz, Brazil. Molecular char- acterization at the Centers for Disease Control, USA, revealed that it was identical to Rickettsia rick- ettsii, which causes Rocky Mountain spotted fever. In the USA, Rocky Mountain spotted fever is a notifiable disease, and, on average, 600-650 cases are reported each year. The majority of such cases have been from the south-eastern and west-south- central states, with the onset of symptoms occurring during May-August. A total of 54.2% of cases have reported a tick bite within 14 days of the appearance of symptoms; the highest incidences are among 5-9- years-olds. The overall case-fatality ratio is 5.2%; however, it is highest among persons aged >40 years (8.2%). Ehrlichia chaffeensis, a new species associated with human disease in the USA, has been identified; approximately 300 cases of illness caused by E. chaffeensis have been documented. Cases have also been identified in Portugal and Mali. A new species of Rochalimaea, R. henselae, has been iso- lated from a febrile man who was seropositive for human immunodeficiency virus (HIV). Based on a wide variety of epidemiological and laboratory evi- dence, including isolation, polymerase chain reaction and serology, R. henselae is most certainly the cause of bacillary angiomatosis, peliosis hepatis and bac- teriaemia in immuno-compromised patients, and cat scratch disease in persons with healthy immune systems. In the Russian Federation approximately 1500 cases of tick-borne typhus are reported annually from central and eastern Siberia. Also, more than 1800 cases of Q fever were reported between 1989 and 1991. Cases of Brill-Zinsser disease have steadily decreased over the years, but pediculosis is prevalent, with 0.5-0.7 persons per 100000 being infected. In Mongolia, foci have been identified where there are greater than expected prevalences of antibody to R. sibirica and Coxiella burnetii. Although these findings do not necessarily iden- tify new foci of rickettsioses, they indicate that coun- tries are beginning to identify specific regions that are endemic for rickettsial diseases. The network of surveillance laboratories was established to facilitate the proliferation of appropriate diagnostic technology at country and regional levels. An increased aware- ness of rickettsioses may encourage local physicians to consider a diagnosis of rickettsial diseases and to start prompt antibiotic treatment. A decrease in mor- bidity and mortality from these diseases should then occur. Considerable effort is still required to make the surveillance system effective; this is justified by the potential gains. The participants at the meeting made the recom- mendations outlined below. * A continual supply of R. conorii, R. prowazekii, and C. burnetii antigens as well as fluorescein-label- led antihuman immunoglobulin must be provided. It would be advisable to prepare antigens to R. tsutsu- gamushi for distribution to laboratories on request. * Action should be taken to develop alternative simple diagnostic tests that would be suitable for use in laboratories where no facilities for the immuno- fluorescence technique are available. * Interchange of sera (both positive and negative) and information between laboratories must be en- couraged in order to promote quality control. The sera should be sent periodically to reference labora- tories to maintain diagnostic quality. * Further training for all the participating labora- tories should be encouraged. This is particularly important for laboratories without experience in immunofluorescence techniques. * WHO should collect and disseminate information on the surveillance of rickettsial diseases throughout the world. WHO Bulletin OMS. Vol 71 1993 295 Memorandum Acknowledgement Dr J.E. McDade (Centers for Disease Control, Atlanta, GA, USA) is thanked for his valuable contributions to the WHO Project on Global Surveillance of Rickettsial Diseases. Annex Participating laboratories that submitted information on rickettsial diseases in 1990-91 and responsible individuals Dr Charmchudhi Chanyasanha Faculty of Public Health, Mahidol University, 420/1 Rajvithi Road, Phyathai, Bangkok 10400, Thailand. Dr V.S. Padbidzi National Institute of Virology, 20-A Dr Ambedkar Road, P.O. Box 11, Pune - 411001, India. Dr Saraljit Sehgal National Institute of Communicable Diseases, 22, Shamnath Marg, Post Box 1492, Delhi-I 10054, India. Dr J. Olson WHO Collaborating Centre for Rickettsial Reference and Research, Viral and Rickettsial Zoonoses Branch, Centers for Disease Control, Division of Viral and Rickettsial Diseases, Atlanta, GA, USA. Dr D. Raoult WHO Collaborating Centre for Rickettsial Reference and Research, Unite des Rickettsies, C.H.U. La Timone, Marseilles, France. Dr I.V. Tarassevich WHO Collaborating Centre for Rickettsial Reference and Research, Laboratory of Rickettsial Ecology, Gamaleya Research Institute of Epidemiology and Microbiology, Gamaleya St. 18, Moscow 123098, Russian Federation. Dr H.H. Barbosa Melles Instituto Adolfo Lutz, Sao Paulo, Brazil. Dr Marcio Antonio M. Galvao Funda,cao Ezequiel Dias, Belo Horizonte, Brazil. Director Instituto-Nacional de Salud, Lima, Peru. Dr L. Jemni Laboratoire Regional de la Sante Publique de Sous- se, 5, Rue de Kairouan, BP 312, Sousse 4002, Tunisia. Dr T.B. Uppal Department of Pathology, Khyber Medical College, Peshawar 21520, Pakistan. Dr T. Messele National Research Institute of Health, Virology and Rickettsiology Division, P.O. Box 1242, Addis Ababa, Ethiopia. Dr M. Dosso Laboratoire de Bacteriologie-Virologie, Faculte de Medecine, C.H.U. de Cocody, Abidjan, Cote d'Ivoire. Dr Chen Xiangrui Institute of Microbiology and Epidemiology, 23 (A) Qilizhuang Road, Fengtai District, Beijing 100071, China. Dr M. Zarour Department of National Hospital of Lattakia, Lattakia, Syrian Arab Republic. Director Central Health Laboratory, Kathmandu, Nepal Dr J. Kazar WHO Collaborating Centre on Rickettsial Reference and Research, Institute of Virology, Dubravska Cesta 9, Bratislava 842 46, Slovak Republic. Dr W. Sixl University of Graz, Graz, Austria. Countries participating in the WHO Project on Global Surveillance of Rickettsial Diseases African Region. Cape Verde, Cote d'Ivoire, Ethiopia, Gabon, Guinea-Bissau. Region of the Americas. Bolivia, Brazil, Colombia, Costa Rica, Ecuador, El Salvador, Guatemala, Mexi- co, Peru, Uruguay, USA. South-East Asia Region. Bangladesh, India, Indone- sia, Mongolia, Myanmar, Nepal, Sri Lanka, Thai- land. European Region. Former Czechoslovakia, France, Greece, Italy, Russian Federation, Switzerland. Eastern Mediterranean Region. Egypt, Iran, Iraq, Pakistan, Syrian Arab Republic, Tunisia. Western Pacific Region. China. WHO Bulletin OMS. Vol 71 1993296