J.E. van Steenbergen 1, A. Leentvaar-Kuijpers 1, J.H.C.T. van den Kerkhof 2
1 National Co-ordinating Centre for Outbreak Management (LCI), Rijswijk, the Netherlands
2 District Public Health Service (GGD), Dordrecht, the Netherlands
About 25 000-50 000 refugees seek asylum in the Netherlands each year. After an immediate juridical assessment 85% to 90% of them are transferred to one of 14 so called reception centres where they are checked for tuberculosis and children and elderly people see a doctor. The vaccination status of children under 18 years is evaluated and brought up to the Dutch standard (diphtheria-pertussis-tetanus, inactivated polio vaccine, measles-mumps-rubella (MMR) and, for refugees, Bacille-Calmette Guérin (BCG). After about four months, refugees are transferred to one of 14 refugee centres or hostels, where they may remain for one to two years until granted official refugee status. Thereafter, they are assisted in seeking appropriate accommodation.
One of the refugee centres is a hostel ship moored in one of Dordrecht’s harbours. It houses 500 refugees, of whom 100 are aged under 18 years and will have been fully vaccinated since arriving in the Netherlands. The vaccination status of adult refugees remains unknown.
About 50 of the refugees in Dordrecht are from the Newly Independent States (NIS) of the former USSR, where diphtheria is rife (1). Cases have arisen in western Europe through contact with cases from the NIS (2). No NIS-related cases of diphtheria have been seen in the Netherlands despite considerable traffic to and from the NIS. Vaccination coverage in the Netherlands is 95% (3). There is some concern about people who were born before universal vaccination was introduced (1952-53) and escaped the epidemic of 1943-44. Less than 40% of people born before 1945 have antibody titres of 0.1 IU/ml or higher (4).
A 27 year old Angolan refugee arrived in the Netherlands in December 1994. He was transferred to the hostel ship in Dordrecht in April 1995 and consulted the centre’s physician for backache, headache, and stomach pain. A chest X-ray in July was normal. In November he was treated for boils. The man was said to have frequent contacts in Rotterdam with newly arrived illegal refugees. He stayed regularly at an unknown address with his officially expelled Angolan girlfriend.
On 2 December, he developed fever, cough, headache, and a sore throat. He was seen by the centre’s physician on 6 December, who prescribed symptomatic treatment. The same evening, however, his symptoms became worse and the family doctor diagnosed severe tonsillitis and pharyngitis (fever 40 oC, tachypnoea, white membrane on one tonsil, extending over the posterior oropharynx). The doctor prescribed an antibiotic to be dispensed the next morning. Two hours later the man died and resuscitation by the family doctor and the ambulance staff was unsuccessful. Haemorrhage from the throat hindered intubation.
Relatives were stunned and became aggressive towards health personnel and centre staff. The local police were asked for assistance and consulted the district public health service (DPHS-GGD) about the possibility of an unnatural death.
Relatives allowed the forensic doctor of the GGD to examine the corpse only superficially. Foamy haemorrhagic mucus, but no membrane was seen in the left nostril. The forensic physician was not allowed to examine the throat. Clear blood and foamy mucus were expelled through the nose when the body was turned.
The next morning, 7 December, the case was presented at the GGD. The medical officer in charge of infectious disease control considered that diphtheria was a possible explanation and urged microbiological investigation. Twelve hours after death, nose and throat swabs were taken and cultured on a selective tellurite plate, with the relatives’ permission. On Friday 8 December, the nasopharyngeal specimens grew colonies suggestive of Corynebacterium diphtheriae (Dr. H.M.E. Frénay, Regional Medical Microbiological Laboratory). Palisading non-motile pleomorphic bacilli with clubbed ends and metachromatic granules were seen on microscopy. Biochemical reactions excluded C. pseudodiphtheriticum. Only staphylococci were cultured from the pharyngeal swab. The tellurite plate with colonies was sent immediately to the National Institute of Public Health and the Environment (RIVM) for a newly developed polymerase chain reaction (PCR) to assess the strain’s toxigenicity. A definite result could not be expected for 24 to 48 hours.
Public health decisions
At this point toxigenicity could not be excluded. Was active intervention with prophylactic antibiotics and booster doses of diphtheria toxoid needed to prevent diphtheria on the boat? If so, to whom should they be given?
The national coordinating centre for outbreak management organised a meeting of professionals on Saturday 9 December, followed by a meeting of governors and administrators. After negotiation with the GGD the relatives agreed to necropsy. The pathologist reported severe erosive inflammation of the upper airways without oedema and haemorrhagic purulent oedematous bronchopneumonia. No macroscopic abnormalities were seen in heart muscle or spleen. No membranes were seen in the airways.
The professionals made the following summary:
· Clinical: The patient died after a short illness with fever, tightness of the chest, and massive bleeding, consistent with pneumonia with inflammatory oedema and a septic or toxic reaction. Diphtheria could not be excluded.
· Microbiological: Suggestive of C. diphtheriae. Toxin production possible.
· Epidemiological: Introduction of diphtheria possible through unknown contacts with people from Angola. There was a continuing outbreak of flu-like illness on the boat. The patient had suffered boils. Secondary bacterial pneumonia after influenza was possible.
· Morbid anatomy: Bacterial pneumonia with sepsis after (viral) upper airway infection. No signs of membranous diphtheria; toxic diphtheria could not be excluded.
The differential diagnosis agreed was: 1. post-influenza staphylococcal pneumonia; 2. streptococcal pneumonia (S. pneumoniae or Group A streptococci); and 3. sudden death from toxic diphtheria.
The meeting advised the board of governors that no immediate large scale intervention was needed but that surveillance should be enhanced and that anyone from the refugee boat with throat complaints, even without fever, should be tested microbiologically. If diphtheria was suspected clinically, penicillin treatment should be given immediately. The GGD was advised to take throat swabs from all relatives of the deceased. Rapid communication of results from reference laboratory (RIVM) to GGD was arranged. The board of administrators agreed with the professional advice but preferred to wait for relatives to ask for screening in order to avoid further unrest. The GGD coordinated the screening and enhanced surveillance in the area with the help of family doctors and paediatricians.
The same day as the board of professionals made their statement (9 December) RIVM reported a negative PCR. A toxigenic strain of C. diphtheriae was therefore most unlikely. Staphylococcus aureuswas cultured from throat, lung, and spleen specimens. No virus could be isolated from necropsy material. RIVM (Dr F. Reubsaet, RIVM/LIS) identified the bacterium initially isolated as corynebacterium CDC group I2, a non-pathogenic corynebacterium resembling C. diphtheriae (5).
Neither the enhanced surveillance nor the screening produced evidence of C. diphtheriae infection or carriage. The final diagnosis was staphylococcal pneumonia with sepsis.
1. CDC. Diphtheria epidemic – New Independent States of the former Soviet Union, 1990-1994. MMWR Morb Mort Wkly Rep 1995; 44: 177-81.
2. Lumio J, Jahkola M, Vuento R, Haikala O, Eskola J. Diphtheria after a visit to Russia.. Lancet 1993; 342: 53-4
3. GHI. Vaccinatiestoestand Nederland. Per 1 januari 1993. Rijswijk, januari 1994.
4. Veer Mvd, Noorle Jansen LM, Nagel J, Steenis G van, Plantinga AD, Rümke HC. Antistofpatroon in een doorsnee van de Nederlandse bevolking. Onderzoek peilstations in 1980 en 1985. RIVM Rapport, Bilthoven, januari 1993.
5. Krech T, Hollis DG. Corynebacterium and related infections. In: Balows A (editor); Manual of Clinical Microbiology, 5th edition. Washington DC: ASM; 1991: 284