Plasmodium falciparum and Mycoplasma pneumoniae co-infection presenting with cerebral malaria manifesting orofacial dyskinesia and haemophagocytic lymphohistiocytosis

Background Malaria is a mosquito-borne infectious disease with diverse clinical manifestations caused by a parasitic protozoan of the genus Plasmodium. Complex inter-relationships between Mycoplasma species and Plasmodium parasites have been previously noted in vitro. This is the first report of Plasmodium falciparum and Mycoplasma pneumoniae co-infection in a human host presenting with cerebral malaria manifesting orofacial dyskinesias and haemophagocytic lymphohistiocytosis. Case presentation A 55-year-old Sri Lankan man with a recent visit to South Africa presented with an acute febrile illness, cough and worsening dyspnoea with alveolar-interstitial infiltrates on chest radiography. Serological evaluation confirmed a diagnosis of Mycoplasma infection. He subsequently developed encephalopathy with orofacial dyskinesia. A diagnosis of severe P. falciparum infection with significant parasitaemia was established. Peripheral blood cytopaenia occurred due to haemophagocytic lymphohistiocytosis in the bone marrow. Complete clinical and haematological recovery was achieved with intravenous artesunate. Conclusions Plasmodium falciparum and Mycoplasma pneumoniae co-infection occurring in vivo manifests clinical features that are plausibly a result of the interaction between the two microorganisms. This is the first report of orofacial dyskinesia in either infection. Electronic supplementary material The online version of this article (doi:10.1186/s12936-016-1517-x) contains supplementary material, which is available to authorized users.


Background
Malaria is caused by protozoa of the genus Plasmodium, of which five species are known to cause human disease; it is transmitted by Anopheles spp. mosquitoes. The clinical manifestations range from uncomplicated infection to severe multisystem affliction with significant mortality. Plasmodium falciparum infections have a high predilection of multisystem manifestations. This case report highlights the unusual combination of Mycoplasma and P. falciparum co-infection presenting with cerebral malaria manifesting orofacial dyskinesias and haemophagocytic lymphohistiocytosis.

Case presentation
A 55-year-old Sri Lankan man employed as a chef in Dubai, United Arab Emirates, presented to the National Hospital of Sri Lanka with fever for five days and associated headache, arthralgia, myalgia and severe prostration approximately 3 weeks after spending 2 months in

Open Access
Malaria Journal *Correspondence: thashichang@gmail.com South Africa as part of his employment. He had been previously well and had not been on chemoprophylaxis for malaria while in South Africa. He has had a worsening non-productive cough and shortness of breath 1 day prior to presentation. On examination, he was pale and had posterior cervical lymphadenopathy. His respiratory rate was 30 cycles/min and he had bilateral diffuse scattered crepitations and rhonchi in both lung bases. Rest of the systems examination was normal.
Initial investigations revealed a marginal neutrophil predominance with thrombocytopaenia (platelets-55,000/mm 3 ) and the chest radiograph showed alveolar-interstitial shadowing. The patient was empirically treated with clarithromycin for 7 days, which resulted in the resolution of the chest symptoms and signs, but with poor resolution of fever. His serum Mycoplasma IgM ELISA (Sigma Aldrich) antibody titre was strongly positive at a dilution of 1/1260 with a repeat titre noted at 1/7560, four weeks after the initial presentation. Given the recent travel history, a blood film was examined for evidence of malaria, but was noted to be negative. Despite initial improvement, progressive thrombocytopenia and worsening anaemia were noted from day 7 of his illness. By day 10, his level of consciousness deteriorated demonstrating abnormal behaviour and worsening drowsiness. Frequent, stereotyped, intermittent orofacial dyskinetic movements, not attributable to any of the drugs administered, were noted (see Additional file 1). Magnetic resonance imaging of the brain was normal. A blood film done at this time demonstrated multiple ring forms of P. falciparum with a parasite load of 300,000/μl. Intravenous artesunate was commenced and the patient demonstrated remarkable clinical improvement with resolution of abnormal movements and improvement of level of consciousness within 24 h. The high-spiking fever which was persistent up to day 12 of illness resolved. However a further decline in the platelet count was noted up to day 14 and a fall in the haemoglobin to 7 g/ dl. His fasting triglyceride level was 405 mg/dl, serum ferritin 25,000 ng/ml and lactate dehydrogenase 1600 U/l. His INR was 1.7; APTT 41s; and fibrinogen level 1.1 g/l. Ultrasound scan of the abdomen demonstrated hepatosplenomegaly. Bone marrow examination demonstrated evidence of resolving haemophagocytosis.
These haematological manifestations subsequently resolved within the next 72 h and the patient made a complete clinical recovery.

Conclusions
This patient highlights a rare combination of a dualinfection manifesting as a biphasic illness with clinical characteristics inherent to each microorganism. The initial presentation was of an acute febrile illness with predominant respiratory involvement and thrombocytopaenia with chest radiography demonstrating interstitial lung inflammation associated with serological confirmation of Mycoplasma infection. The subsequent phase was of worsening peripheral blood cytopaenia and neurological manifestations despite resolution of respiratory features caused by severe P. falciparum infection.
Complex inter-relationships between Mycoplasma species and Plasmodium parasites have been previously noted in vitro and in animal models [1,2]. The effects of other microbial agents provoking host stress response to activate latent pathogenic Mycoplasma have been investigated in animal studies [1]. Accelerated growth of contaminant Mycoplasma species in cultures of P. falciparum had resulted in subsequent reduction in Plasmodium parasitaemia [2]. This is the first report of P. falciparum malaria and Mycoplasma co-infection in a human host. It is plausible that this patient acquired latent infections of both organisms in South Africa and the eradication of Mycoplasma may have led to a surge of P. falciparum parasitaemia, which had been suppressed by Mycoplasma, predisposing the patient to develop cerebral malaria. The incubation period for presentation in this patient is unusually long for P. falciparum malaria. The authors hypothesize that this long incubation period may be due to the suppression of P. falciparum parasitaemia due to Mycoplasma coinfection. It is extremely unlikely that he could have acquired the infection in Sri Lanka as the last endemic case was reported in October 2012.
The cerebral manifestations of P. falciparum infection are diverse, ranging from encephalopathy, seizures, dysconjugate ocular movements to psychiatric manifestations and post-malaria neurological syndromes [3]. However orofacial dyskinesias as observed in this patient have not been previously documented in malaria. Similarly, although neurological manifestations such as choreoathetosis have been reported in Mycoplasma infection [4], orofacial dyskinesia has not been described. It is plausible that the complex interaction between the two organisms may have predisposed to this atypical neurological manifestation, which is clinically significant since orofacial dyskinesia has been increasingly recognized to characteristically occur in NMDAR-antibody encephalitis [5,6] and this case description adds to its differential diagnosis of a comatose patient presenting with movement disorders, particularly in the orofacial region.
The progressive cytopaenia in this patient was attributed to haemophagocytic lymphohistiocytosis (HLH). Although severe malaria per se can cause cytopaenia, HLH was considered more likely in this patient because the cytopaenia developed during the resolution phase of malaria and was associated with hypofibrinogenaemia, hyperferritinaemia, hypertriglyceridaemia and a high