Special Pathogens Unit (SPU)

Overview

The Special Pathogens Unit of the National Institute for Communicable Diseases is primarily responsible for the laboratory diagnosis and investigation of biohazard class 3 and 4 viruses, including the haemorrhagic fever viruses and arboviruses. The Unit operates a maximum biocontainment laboratory (BSL-4) where workers are protected in all-enclosing plastic suits with breathing air supplied through hoses. This is the only laboratory of its kind on the continent. Class 4 viruses known to occur in Africa include Marburg, Ebola, Rift Valley fever, Crimean-Congo haemorrhagic fever, Lassa fever-related arenaviruses, and hantaviruses. The Special Pathogens Unit is also responsible for the laboratory confirmation and investigation of human rabies and other biohazard class 3 viruses. The Unit complies to the ISO15189:2003 standard for medical laboratories for arbovirus serology and virus isolation tests (SANAS: M00029B).

Hisotry of the Unit

The Poliomyelitis Research Foundation (PRF) in Johannesburg, which was the main centre for medical virology in South Africa, was consulted by scientists abroad when Marburg disease first appeared in Europe in 1967 in association with monkeys imported from Africa, and again in 1969 when the rodent-borne Lassa fever first appeared as a fatal disease of missionary nurses in West Africa. In 1975, two young Australian tourists became sick in South Africa with what proved to be Marburg haemorrhagic fever after they had been hitchhiking in Zimbabwe, and a nurse became infected while attending the patients in Johannesburg. The sudden emergence of these dangerous new viruses in Africa prompted the development of maximum-security laboratories, and health authorities in South Africa felt the need to construct such a laboratory in the country.

In April 1976, the laboratories of the PRF were transferred to the State Department of Health and reconstituted as the National Institute for Virology (NIV), with Professor OW Prozesky being appointed as the first Director of the new Institute. Professor Prozesky, the Secretary for Health, Mr J de Beer, an architect from the Department of Public Works, Mr CF Beyers, and a consultant engineer, Mr AP Thompson, undertook a tour of microbiological institutes abroad, and on the basis of the information they gathered a biosafety level 4 (BSL4) laboratory was planned and built at NIV. Construction was completed in 1979, and in January 1980 Dr R Swanepoel from Zimbabwe was appointed as the head of a new Special Pathogens Unit to operate the BSL4 laboratory for the purpose of providing a diagnostic and investigatory service for viral haemorrhagic fevers in southern Africa. Within months, a Department of Health Medical Ecology Unit, responsible for monitoring plague activity in rodents, was incorporated into the SPU. In 1981, the Arbovirus Unit at NIV was made part of the SPU, and in 1983 responsibility for the diagnosis and investigation of rabies was allocated to the Unit.

In its second month of operation, in February 1980, the SPU became involved in the investigation of an outbreak of Marburg haemorrhagic fever in Kenya in association with the Special Pathogens Branch of the Centers for Disease Control in Atlanta, USA, leading to lasting cooperation between the two laboratories. In 1981, the first case of Crimean-Congo haemorrhagic fever (CCHF) was recognized in South Africa, and for the next decade work on this disease dominated the research programme of the SPU.

By the end of 2003, the SPU had investigated 4 570 blood and other samples from 2 788 suspected cases of viral hemorrhagic fever in South Africa and its immediate neighbours, plus a further 4 687 specimens from 3 091 patients from 22 countries in the rest of Africa, and 10 countries in Asia and Europe. Important diseases diagnosed included Marburg haemorrhagic fever, Ebola haemorrhagic fever, CCHF, Lassa fever, Rift Valley fever, yellow fever, dengue, West Nile fever, chikungunya and o’nyongnyong. However, the majority of the suspected cases of haemorrhagic fever proved to be more common vaccine-preventable or treatable diseases, and the number of patients investigated does not reflect the actual extent of the epidemics involved. In the most extreme example 4 600 people are estimated to have died in southern Sudan in 1999 from what the SPU diagnosed as louse-borne relapsing fever, which could readily be controlled through the use of an inexpensive antibiotic and insecticide. SPU staff has participated in many missions abroad, sometimes as members of international teams organized by the WHO to respond to epidemics, or to conduct ecological studies to determine the source of infectious agents in nature, such as Marburg and Ebola viruses. Many thousands of specimens from domestic and wild animals and insect vectors have been tested in the course of such investigations. Major missions included trips to the Democratic Republic of the Congo, Gabon, Sudan, Kenya, Somalia, Uganda, Sierra Leone, Guinea, Liberia, Afghanistan and Saudi Arabia.

Another busy time for the Unit was during the last 2 months of 1996, when a major outbreak of CCHF among workers at an ostrich abattoir caused the European Union to ban importation of all ostrich products from South Africa, thereby threatening the continued existence of a major industry. While still testing samples from hundreds of abattoir workers, the SPU had to study the nature of experimental CCHF infection in ostriches to provide information so that the Department of Veterinary Public Health could promulgate regulations designed to prevent the virus getting into ostrich products, thus making it possible for the ban to be lifted. Meantime, Ebola haemorrhagic fever was diagnosed in a nurse in Johannesburg, and a frantic search ensued to locate the source patient who proved to be a doctor from Gabon who had sought treatment for his illness in South Africa. This in turn led to a major exercise to identify and monitor health care workers and others who had been in contact with the 2 patients. Tragically, the nurse died but further spread of the infection was prevented.

In 2003 the SPU became involved in performing diagnostic tests on suspected cases of severe acute respiratory syndrome (SARS), but fortunately the disease was not confirmed in southern Africa. Most recently the Unit has played an important role in investigating the occurrence of human infections with highly pathogenic avian influenza A H5N2 virus followed by an outbreak of the disease in ostrich population in the Eastern Cape in May 2004.

In 2008, the Unit was involved with the laboratory and field investigation of a local nosocomial outbreak of a previously unreported arenavirus haemorrhagic fever during September and October 2008. The index case was a female travel guide based in Lusaka, Zambia. She was evacuated for medical attention to a hospital in Johannesburg, South Africa after a 10 days of illness which was at the time clinically diagnosed as septicaemia, possibly typhoid. The patient passed away the day after being admitted to the Johannesburg hospital without a confirmed diagnosis. Three secondary cases involved a paramedic that was attending the index case during the medical evacuation, a nurse who cared of the index patient and a hospital cleaner who cleaned the ward. One tertiary case, and the only survivor of the outbreak, was a nurse that had contact with the paramedic. Once the epidemiological link between case 2 and the index case was realized, extensive differential laboratory testing for VHF was carried at SPU- NICD on specimens for cases 2, and also 3, but without any positive results. The first indication that an arenavirus was the etiological agent followed immunohistochemistry testing of liver biopsies by the CDC. These results were confirmed by PCR and virus isolation at SPU and the CDC. Subsequently all cases were confirmed by PCR and virus isolation. IgM seroconversion could only be shown in case 5. Specimens for the index case were not available locally and were forwarded from Zambia for retrospective testing to the CDC. In collaboration with the Colombia University and CDC the full genome sequencing study was undertaken which results confirmed that the outbreak was caused by a novel Old World arenavirus.

Contact Us

Staff

Diagnostic Services

Publications

Contact us

Please direct any queries via one of the following:

Postal address: Private Bag X4, Sandringham 2131, South Africa

Physical address: 1 Modderfontein road, Sandringham 2131, South Africa

Queries	Telephone	Email
General	+27113866382
Laboratory	+27113866336 (Special Pathogens) +27113866391 (Arbovirus) +27113866376
Medical (outbreaks, VHF, rabies or arboviral disease)	+27828839920 (24 Hour NICD Hotline for clinical Advise) +27113866336

Staff

Head of Department
Prof JT Paweska (BVSc, DVSc, Doctor habilitatus)

Deputy
Dr J Weyer (PhD)
Medical Scientist

Consultant
Prof R Swanepoel (BVSc PhD DTVM MRCVS)

Departmental Secretariat
Mrs LJ Dos Santos

Special Pathogens Laboratory

Mrs PA Leman, PA (BSc Hons)
Medical Scientist / Laboratory Manager

Mrs AA Grobbelaar (MSc)
Medical Scientist

Miss CA Le Roux (BSc Hons)
Medical Scientist

Mrs J Croft (Dip Med Lab Tech)
Medical Technologist

Mr CT Ndou (BSc)
Medical Technician

Mr NB Magome General worker)
Mrs SG Nkomo(General worker)

Arbovirus Laboratory

Mr A Kemp (MSc)
Medical Scientist / Laboratory Manager

Mr P Jansen van Vuren (MSc)
Medical Scientist

Mrs MG Lekhuleni (Dip Med Lab Tech)
Medical Technologist

Mr S Serero
Laboratory Assitant

Mr TE Chaane
Laboratory Assitant, Intern

Mr R Nkoana (General Worker)
Mr D Tigedi (General Worker)

Animal Unit

Mrs B Mogodi (Dip Animal Tech)
(Chief Animal Technologist)

Maseko, J (General Worker)
Seema, L (General Worker)

Sibiya, S (General Worker)
Mavhungu, MS (General Worker)

BSL-4 Engineering / Workshops

Mr Z Masuku (B Ing, LTS Consultant)
Mr R Mabilo (Artisan)
Mr P Mokoena (Assistant Artisan)

Diagnostic Services

The Special Pathogens Unit is the referral laboratory for laboratory confirmation of viral haemorrhagic fevers, arboviral disease and rabies (in humans). Serology and virus isolation of arboviruses are performed in compliance to ISO 15189:2003 (SANAS accreditation number: M00029B).
The following diagnostic tests are available:

Table 1: Diagnostic tests for viral haemorrhagic fevers and other biosafety level 2 and 4 pathogens

Pathogen	Specimen required	Test/s performed
Ebola virus Marburg virus Lassa virus Crimean congo haemorrhagic fever virus Hantaviruses	Clotted blood	ELISA, IgM Indirect immunofluoresence, IgG and IgM PCR Virus isolation
SARS coronavirus	Clotted blood Throat swabs Stool	PCR ELISA

Table 2: Diagnostic tests for arboviral disease

Pathogen	Specimen required	Test/s performed
Chikungunya virus Dengue virus Rift Valley fever virus Sindbis virus West Nile virus Yellow fever virus	Clotted blood (or serum) (Cerebrospinal fluid for encephalitic cases)	ELISA, IgM Indirect immunofluoresence, IgG and IgM PCR Virus isolation

Table 3: Diagnostic tests for human rabies

Specimen	Test/s performed	Comments
Saliva (and Cerebrospinal fluid)	PCR Virus isolation	Only clinical patients Saliva preferred
Serum (or clotted blood)	Indirect immunofluoresence	In addition to saliva/cerebrospinal fluid for clinical patients For post vaccinal immunity determination
Brain	Direct immunofluoresence PCR Virus isolation	Post mortem testing Gold standard

Table 4: Diagnostic tests for rickettsia infection (Tick bite fever)

Pathogen	Specimen required	Test/s performed
Rickettsia conorri (Tick bite fever)	Whole blood (EDTA/purple cap)	PCR* Indirect immunofluoresence
Other Rickettsia	Whole blood (EDTA/purple cap)	PCR*

* PCR has diminished sensitivity when patient has received antibiotic treatment

Publications

Recent publications by members of staff

Publications by members of SPU staff during 2008

Botha EM, Markotter W, Wolfaardt M, Paweska JT, Swanepoel R, Palacios G, Nel LH, Venter M. Genetic determinants of virulence in pathogenic lineage II West Nile virus strains. Emerging Infectious Diseases 2008; 14: 222-230.

Burt FJ, Paweska JT, Ashkettle B, Swanepoel R. Genetic relationship among southern African Crimean-Congo haemorrhagic fever virus isolates and evidence of reassortment. Epidemiology and Infection. (In press).

Burt FJ, Paweska JT, Ashkettle B, Swanepoel R. Genetic relationship among southern African Crimean-Congo haemorrhagic fever virus isolates and evidence for occurrence of reassortment. Epidemiology and Infection. (In press).

Coetzee P, Weyer J, Paweska JT, Markotter W, Burt FJ, Nel LH. Use of a molecular epidemiological database to track human rabies case histories in South Africa. Epidemiology and Infection 2008; 136: 1270-1276.

Evans A, Gakuya F, Paweska JT, Tostal M, Akoolo L, Van Vuren PJ, Manyibe T, Macharia JM, Ksiazek G, Feikin DR, Breiman RF, Njenga MK. Prevalence of antibodies against Rift Valley fever virus in Kenyan wildlife. Epidemiology and Infection 2007; 136; 1261-1269.

Evans A, Gakuya F, Paweska JT, Rosta, M, Akoolo, Jansen van Vuren PJ, Manyibe T, Macharia JM, Ksiazek TK, Feikin DR, Breiman R F, Karriuki Njenga M. Prevalence of antibodies against Rift Valley fever virus in Kenya wildlife. Epidemiology and Infection 2008; 136: 12-61-1269.

Heise MT, Whitmore A, Thompson J, Grobbelaar AA, Paweska JT, Madrick K, White L, Swanepoel R, Burt FJ. An alphavirus replicon derived candidate vaccine against Rift Valley fever virus. Epidemiology and Infection. (In press).

Jansen van Vuren P, Paweska JT. Laboratory safe detection of nucleocapsid protein of Rift Valley fever virus in human and animal specimens by a sandwich ELISA. Journal of Virological Methods. (In press).

Le Roux CA, Kubo T, Grobbelaar AA, Jansen van Vuren P, Weyer J, Nel LH, Swanepoel R, Morita K, Paweska JT. Development and validation of a real-time reverse transcription-loop-mediated isothermal amplification assay for rapid detection of Rift Valley fever virus in clinical specimens. Journal of Clinical Microbiology. doi:10.1128/JCM.01412-08.

Markotter W, van Eden C, Kuzmin IV, Ruprecht CE, Paweska JT, Swanepoel, R, Fooks, A.R., Sabeta, C.T., Cloquet, F., Nel, L. H. Epidemiology and pathogenicity of African bat lyssaviruses. Dodet B, Fooks AR, Müller T, Tordo N, and the Scientific & Technical Department of the OIE (eds). Towards the Elimination of Rabies in Eurasia. Dev. Biol. Basel, Karger, 2008, vol. 131, pp. 317-325.

Njenga K M, Paweska J, Wanjala R, Rao C Y, Weiner M, Omballa V, Luman ET, Mutonga D, Sharif A, Panning M, Drosten C, Feikin DR, Breiman RF. Using field qRT-PCR test to rapidly identify highly viremic Rift Valley fever cases. Journal of Clinical Microbiology. (In press).

Paweska JT, Jansen van Vuren P, Kemp A, Buss P, Bengis RG, Gakuya F, Breiman RF, Kariuki MN, Swanepoel R. Recombinant nucleocapsid-based ELISA for detection of IgG antibody to Rift Valley fever virus in African buffalo. Veterinary Microbiology 2008; 127: 21-28.

Paweska JT. Host gene expression triggered by West Nile virus infection. In: RNA viruses: response to infection. World Scientific Publications. (In press).

Swanepoel R, Paweska JT. Rift Valley fever. In: Zoonoses. 2nd Edition. Palmer SR, Soulsby EJL, Torgerson P, Brown D (eds). Oxford University Press. (In press).

Swanepoel R, Paweska JT. Crimean-Congo haemorrhagic fever. In: Zoonoses. S.R. Palmer, E.J.L. Soulsby, P. Torgerson and D. Brown (eds). Oxford University Press. (In press).

Swanepoel R, Burt FJ. Flaviviruses of veterinary importance. In: Encyclopedia of Virology. 3rd Edition. Mahy B, Van Regenmortel M (eds). Elsevier. (In press).

Swanepoel R, Burt FJ. Bunyaviridae. In: Principles and Practice of Clinical Virology. 6th Edition. Zuckerman A, Banatvala J, Griffiths P, Mortimer P, Schoub B (eds). Chichester: John Wiley and Sons. (In press).

Venter M, Burt FJ, Leman PA, Blumberg L, Fikl H, Paweska J, Swanepoel, R. Cytokine induction following laboratory acquired West Nile Virus meningo-encephalitis. New England Journal of Medicine. (In press).

Venter M, Human S, Zaayman D, GerdesT, Williams J, Steyl J, Leman P, Paweska J, Setzkorn H, Rous G, Murray S, Parker R, Donnellan C, Swanepoel R. Lineage 2 West Nile virus as a cause of fatal neurological disease in horses in South Africa. Emerging Infectious Diseases. (In press).