Sudden death caused by Staphylococcus aureus carrying Panton–Valentine leukocidin gene in a young girl

Abstract

Staphylococcus aureus carrying the Panton–Valentine leukocidin (PVL) gene could be the source of both recurrent furunculosis or abscesses and severe infections, mainly necrotising pneumonia. We present the case of a young girl from consanguineous parents who died suddenly. The postmortem examination revealed necrotising pneumonia due to a PVL producing Staphylococcus aureus strain, raising the question of the role of the host’s immune status in this infection.

Case presentation

We report the case of a young girl, the third child of parents who were first cousins, who died suddenly. The parents originally came from an isolated village in Africa. The patient had never travelled outside her home. No illness relating to the consanguinity could be observed. No unusually severe infections or disease were documented in the family. Twenty-four hours before dying, the girl developed an influenza-like syndrome with fever and cough. However, her general condition was good and the level of fever was low (38–38.5°C). The parents were not worried when they put their daughter to bed, as she had been eating, playing and behaving normally. However, the following morning she was found dead in her bed.

Investigations

Postmortem blood examinations revealed a leucocyte count of 2900/mm³, 81% neutrophils, and a marked inflammatory syndrome (C reactive protein 220 mg/l, procalcitonin 37.6 ng/ml). Serologic testing for HIV was negative. There was no evidence of acute influenza. Samples of pleural fluid and blood culture yielded a strain of Staphylococcus aureus which was susceptible to methicillin. Detection of the genes encoding Panton–Valentine leukocidin was positive. The strain was negative for the other toxins: enterotoxins (staphylococcal enterotoxin A (SEA), SEB, SEC), toxic shock syndrome toxin 1 (TSST1), and exfoliatins (ETA, ETB). Postmortem computed tomography scan revealed multiple bilateral cavitary lung lesions. Examination of the parents revealed no chronic furunculosis. No abnormality of the phagocytic cells or complement deficiencies could be found during the postmortem blood examinations.

Discussion

Panton–Valentine leukocidin (PVL) is one of many toxins produced by S aureus which targets polymorphonuclear cells, monocytes, and macrophages.^1,2 PVL is a bi-component exotoxin composed of two polypeptides, LukS and LukF, with varying cellular affinities and destructive capability, even when the strain may be otherwise sensitive to antibiotics such as methicillin. PVL induces a process of necrosis by stimulating granulocyte synthesis of inflammatory mediators. PVL also participates in the extension of the infection by inhibiting phagocyte functions and provoking destruction of these granulocytes.³ Disease caused by PVL producing S aureus is rarely life threatening, presenting as recurrent furunculosis or abscesses. S aureus may be either sensitive or resistant to methicillin, and it can be difficult to eradicate among carriers. However, necrotising pneumonia has been associated with PVL producing staphylococci. PVL has been found in 85% of S aureus strains isolated from patients with community acquired pneumonia.⁴ PVL positive S aureus necrotising pneumonia is associated with a very high fatality rate of 56%, with most of the patients being young, immunocompetent, and otherwise healthy.⁵

The pneumonia can occur following viral respiratory infections, especially influenza. Early appropriate antibiotic treatment is thus crucial. Early administration of intravenous immunoglobulin (IVIg) and antitoxin antibiotics (clindamycin of linezolid) may be helpful in PVL associated diseases. Familial carriage of S aureus has been shown to be a risk factor for subsequent infection with the same organism in neonates and infants. Because postmortem specimens are rarely cultured and the disease is not notifiable, its true incidence remains unknown. Early diagnosis of necrotising pneumonia is very difficult, especially in young, fit people. Pyrexia, myalgia, chills, and occasionally diarrhoea imply non-specific viral illness but, equally, can indicate the production of other staphylococcal toxins.

Little attention has been paid to the possible genetic predisposition to infection with PVL producing staphylococci. Our patient was from a consanguineous family and was significantly younger than previously reported cases. Unfortunately, the possibilities of consanguinity were not investigated in most previous case reports and series. A combined action of several virulence factors enables S aureus to cause disease. However, infection with PVL producing staphylococci can cause diseases ranging from superficial skin infections to deep seated and systemic conditions such as severe bone and joint infections, septic shock, and necrotising pneumonia. The immune status of the host could be important. No studies have focused on the role of immunity in the pathogenesis of this disease. Recently, a high predisposition to severe S aureus infection in some mouse models suggested a possible genetic predisposition.⁶ It may thus involve a specific pathway. Indeed, an increasing number of molecularly proven primary immunodeficiency diseases are being found that confer predisposition to a single type of infection.⁷ The identification of a human S aureus susceptibility gene should improve our understanding of the immunological pathways involved in the protective immunity to PVL producing staphylococci.

Finally, our case raises questions over the incidence of infection with PVL producing staphylococci in cases of sudden infant death syndrome (SIDS). Blackwell et al found that more than 10% of SIDS cases had S aureus in a sterile site.⁸ The value of unexpected positive microbiological findings in SIDS was demonstrated.⁹ About 15% of SIDS cases could be explained on the sole basis of these findings—that is, most were pneumococcal or meningococcal meningitis and/or septicaemia. An increased throat carriage of S aureus, coliforms, and group B streptococci could be found in a comparison with normal healthy age matched infants. Indeed, staphylococcal toxins have been demonstrated in the tissues of a large proportion of babies deemed to have died of SIDS. However, to our knowledge, PVL has not been specifically studied in a cohort of SIDS cases. It has been hypothesised that pro-inflammatory cytokine responses to bacterial infection and/or toxins play a role in triggering a “cytokine storm” resulting in SIDS.⁸ Support for this is found in the relationship between pro-inflammatory gene polymorphism frequencies (for example, interleukin 6 (IL6) and tumour necrosis factor α (TNFα)) in SIDS cases compared with controls. Comparison of the isolation rates of key bacteria (for example, S aureus) that could play a role in this condition may provide further support for this hypothesis.

Learning points

• There is a very high fatality rate associated with Panton–Valentine leukocidin (PVL) positive S aureus necrotising pneumonia.

• Young, immunocompetent and otherwise healthy children who are affected may have a genetic predisposition to infection with PVL producing staphylococci.