Guillain-Barre Syndrome in a female patient with Falciparum Malaria Infection-a rare case scenario

doi:10.21203/rs.3.rs-4808884/v1

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Case Report

Guillain-Barre Syndrome in a female patient with Falciparum Malaria Infection-a rare case scenario

https://doi.org/10.21203/rs.3.rs-4808884/v1

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Background

Malaria is an infectious disease caused by Plasmodium parasites, transmitted to humans by infected female Anopheles mosquitoes. Five Plasmodium species infect humans: P. vivax, P. falciparum, P. ovale, P. malariae, and P. knowlesi. Guillain-Barré Syndrome (GBS) is an inflammatory condition leading to paralysis, muscle weakness, autonomic dysfunction, respiratory failure, and sensory symptoms. GBS typically follows an infection with Campylobacter bacteria, commonly found in undercooked poultry, but is rarely associated with malaria.

Clinical presentation

A 16-year-old female presented with a 4-day history of progressive inability to move her lower extremities, accompanied by 8 days of persistent non-radiating back pain and fatigue. She also had fever and headache for 13 days and was treated with Quartum 4 tablets, taken twice daily for 3 days. Motor examination revealed a motor score of 1/5 in both lower extremities and 4/5 in upper extriemity, decreased muscle tone, and absent deep tendon reflexes (0/4). After completing treatment in the medical ward, she was discharged with improvement, showing motor examination power of 4/5 and reflexes of 1/4.

Discussion

Guillain-Barré Syndrome (GBS) is an acute paralytic illness often triggered by infections, particularly viral ones. It is the leading cause of sudden muscle weakness and paralysis, typically following respiratory or gastrointestinal infections, with Campylobacter jejuni being the most common cause. GBS progresses rapidly, with symptoms worsening over days to weeks and peaking within four weeks. It is characterized by progressive muscle weakness starting in the legs, spreading upwards, areflexia, and sensory symptoms like tingling or numbness in the feet and hands. Electrophysiological studies can confirm nerve involvement but are not always necessary if clinical and CSF findings strongly indicate GBS.

Conclusion.

In conclusion, while malaria is an exceptionally rare cause of Guillain-Barré Syndrome (GBS), it should be considered in patients with recent malaria infection who present with GBS symptoms.

Guillain-Barré Syndrome

Plasmodium Falcifarum

Paresis

Malaria is an infectious disease caused by parasites of the Plasmodium genus. It is transmitted to humans through the bite of an infected female Anopheles mosquito. There are five species of Plasmodium that can infect humans: P. vivax, P. falciparum, P. ovale, P. malariae, and P. knowlesi. ^[1.2] The global burden of malaria has been increasing in recent years. In 2017, approximately 219 million people were affected by malaria, leading to 435,000 deaths worldwide. The overall global mortality rate from malaria ranges from 0.3–2.2%. However, in tropical countries, the mortality rate for severe forms of the disease rises significantly, ranging from 11–30%. ^{[3, 4]}

The Plasmodium falciparum parasite is primarily responsible for the majority of neurological complications associated with malaria. However, Plasmodium vivax can also cause seizures in children and lead to neurological complications such as Guillain-Barré Syndrome (GBS). ^{[5, 6]}. Other neurological manifestations of malaria include psychiatric symptoms, seizures, myelopathies, peripheral neuropathies, myopathies, extrapyramidal syndromes, intracranial hemorrhage, and, less commonly, reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES). Neurological issues can also arise as side effects of antimalarial treatments. ^{[7, 8]}.

Guillain-Barré Syndrome (GBS) is an inflammatory condition characterized by generalized paralysis, bulbar muscle weakness, autonomic dysfunction, respiratory failure, and the presence or absence of sensory symptoms. It most commonly occurs following an infection with Campylobacter, a type of bacteria often found in undercooked poultry. However, its occurrence following malaria is very rare. ^{[9, 10]}

The occurrence of Guillain-Barré Syndrome (GBS) associated with malarial infection is very rare, with only a few cases documented in the literature. Here, we present a case of acute flaccid paraparesis of the lower extremities in a patient with a positive Plasmodium malaria infection, which improved with steroid treatment.

A 16-year-old female presented with a chief complaint of progressive inability to move her extremities over the past 4 days which started in lower extremity. She also reported an 8-day history of persistent non-radiating back pain and fatigue. Additionally, she had experienced fever and headache for 13 days and was started on Quartum 4 tablets, taken twice daily for 3 days. Despite this, the fever persisted with intermittent headaches. She reported no shortness of breath, cough, vomiting, or lower urinary symptoms. There was no recent history of respiratory, urinary tract, or gastrointestinal infections, nor any personal or family history of chronic illnesses such as diabetes mellitus, hypertension, or cardiac disease. She was not taking any other medications.

On physical examination, the patient appeared anxious but showed no signs of cardiorespiratory distress. Her blood pressure was labile, ranging from 160/100 to 100/80 mmHg, and her pulse rate ranged from 90 to 116 beats per minute, indicating autonomic dysfunction. Her respiratory rate was 24 breaths per minute, temperature was 37.7°C, BMI was 18.4, and oxygen saturation was 95% on room air. She was alert and oriented to time, place, and person with a Glasgow Coma Scale (GCS) score of 15/15. Pupils were reactive bilaterally and mid-sized. Motor examination revealed a motor score of 1/5 in both lower extremities and 4/5 in upper extremity, decreased muscle tone, absent deep tendon reflexes (DTR) of 0/4, and a negative Babinski sign, consistent with lower motor neuron injury. There were no sensory and cranial nerve abnormalities except for hyperesthesia. Meningeal signs were negative. Conjunctivae were pink, and sclerae were non-icteric. Heart sounds S1 and S2 were well heard with no murmurs or gallops. The chest was clear and resonant. Abdominal examination revealed no masses or organomegaly, and there was no edema in the extremities.

Laboratory investigations included a complete blood count (CBC) showing a white blood cell (WBC) count of 10,600/mm³, hematocrit (HCT) of 32.2%, mean corpuscular volume (MCV) of 90, and platelets of 160,000/mm³. Blood film confirmed the trophozoite stage of Plasmodium falciparum, and the rapid diagnostic test yielded similar results. Cerebrospinal fluid (CSF) analysis via lumbar puncture showed a normal WBC count (2 WBC/HPF) but elevated albumin level (90 mg/dL) and negative gram staining. Urinalysis and stool occult blood test results were normal, with no parasites or pus cells identified. Random blood sugar (RBS) was 183 mg/dL, and tests for Anti-Nuclear Antibody (ANA), Antineutrophilic Cytoplasmic Antibody (ANCA), and Antiphospholipid Antibodies (APLA) were normal. Renal function tests (RFT), serum electrolytes, coagulation profile, and erythrocyte sedimentation rate (ESR) were all normal. Serology for syphilis was negative. Chest radiograph, echocardiogram, EKG, and carotid Doppler were normal.

The diagnosis of lower motor neuron lesion secondary to Guillain-Barré Syndrome (GBS) and Plasmodium falciparum malaria was considered. The patient was admitted to the adult ICU and managed with artesunate 2.4 mg/kg at 0, 12, 24, 48, 72, and 96 hours. She received labetalol infusion as needed if blood pressure exceeded 160/110 mmHg. The patient was catheterized, and her urine output was 0.8 mL/kg/hr. She showed improvement, with motor examination returning to 3/5 in lower and 5/5 in upper extremity, and was transferred to the ward after 10 days. The patient's family was advised on the definitive management of GBS with IV immunoglobulin (IVIG) and plasmapharesis; however, they were unable to afford it. After completing treatment in the medical ward, stayed for one week, the patient was discharged with improvement with motor examination power 4/5 and reflex ¼( hypporeflexia). She continued home physiotherapy and was advised to adhere to follow-up visits. She has been seen in the medical referral clinic on several occasions within 2 months with no signs of neurologic injury with motor examination power 5/5 and reflex of 2/4.

Guillain-Barré Syndrome (GBS) is a well-known acute paralytic illness that often arises after infections, especially viral ones. It's the leading cause of sudden muscle weakness and paralysis, usually following respiratory or gastrointestinal infections, with Campylobacter jejuni being the most common culprit.^{[7, 11]}Besides viruses, GBS can also be triggered by bacterial infections like Mycoplasma, Haemophilus influenzae, and Rickettsia rickettsii, as well as protozoal infections such as Leishmania donovani and Plasmodium species, including both Plasmodium falciparum and Plasmodium vivax. In rare instances, GBS has been associated with inflammatory conditions like sarcoidosis and the use of certain medications. ^{[11.12.13.14]}

Guillain-Barré Syndrome (GBS) is an immune-mediated, acute inflammatory disorder affecting nerves globally and at any age, where the immune system mistakenly targets nerve antigens due to molecular mimicry. ^{[11, 12]} In cases associated with malaria, the immune response during the parasite's asexual stage, involving cytokine release, is believed to cause nerve damage, though the exact mechanism is not fully understood. Immune-mediated damage is thought to drive the development of GBS, with the inflammation triggered by cytokines affecting the axons and leading to demyelination. This could explain the link between malaria infection and GBS. Another possible explanation is that GBS might result from occlusion of the vasa nervorum by malaria parasites or immune complexes.^{[7, 13, 14]}

Guillain-Barré Syndrome (GBS) typically develops rapidly, with symptoms worsening over days to weeks and peaking within about four weeks. Key features include progressive muscle weakness that starts in the legs and spreads upwards, areflexia (absence of reflexes), and sensory symptoms like tingling or numbness, usually beginning in the feet and hands. Patients may also experience severe muscle pain, autonomic dysfunction (affecting heart rate, blood pressure, sweating, and digestion), cranial nerve involvement (leading to facial weakness, swallowing difficulties, or eye movement issues), and in severe cases, respiratory problems requiring mechanical ventilation. ^{[11, 14]} In this case, symptoms began with lower limb weakness and areflexia, progressing quickly to flaccid paraparesis, and autonomic dysfunction, and the patient also had AFI symptoms with positive smear, a condition often associated with malaria infections.

The clinical symptoms of malaria vary depending on the parasite type and infection severity. Common symptoms include cyclical fever with chills and sweating, severe headache, intense muscle and joint pain, fatigue, nausea, vomiting, abdominal pain, and sometimes diarrhea. Anemia and jaundice due to liver involvement are also common. Severe malaria, which demands urgent care, may present with impaired consciousness, respiratory distress, acute renal failure, severe anemia, hypoglycemia, and shock. Symptoms typically appear 7 to 30 days after a mosquito bite, though they can manifest later. ^{[3, 6, 7]}

Although electrophysiological studies are useful for confirming nerve involvement, they are not always necessary if clinical and CSF findings are strongly indicative of Guillain-Barré Syndrome (GBS). Key indicators of GBS include progressive muscle weakness in multiple limbs, areflexia (absent reflexes), and possibly sensory changes, pain, autonomic dysfunction (such as heart rate variability and blood pressure fluctuations), or cranial nerve issues. CSF analysis showing elevated protein levels with a normal white blood cell count (cyto-albuminogenic dissociation) supports the diagnosis, especially when there is a recent history of infection.^{[11, 15, 16, 17]} In this case, the neurological signs suggested progressive lower motor neuron paralysis with areflexia, autonomic dysfunction, and paraesthesia, while CSF analysis confirmed cyto-albuminogenic dissociation. The patient also had confirmed Plasmodium falciparum malaria. Typically, the interval between fever and weakness ranges from 1 to 6 weeks, but this case showed a seven-day delay. This report illustrates that GBS may follow Plasmodium falciparum malaria.

Treatment of Guillain-Barré Syndrome (GBS) primarily involves supportive care, managing symptoms, and addressing the autoimmune response. Intravenous Immunoglobulin (IVIG) and Plasma Exchange (plasmapheresis) are commonly used first-line therapies to reduce the immune attack on the nerves. Although GBS can resolve without these treatments like this case, recovery may be slower and more variable. Supportive care is crucial, especially for respiratory management, with mechanical ventilation required in severe cases. Pain management strategies help alleviate severe muscle pain, while physical therapy is essential for improving strength, mobility, and function, and preventing complications from immobility. ^[11.14.17] In this case, the patient was managed with gabapentin for pain, physiotherapy, and labetalol for autonomic dysfunction; she did not require mechanical ventilation.

In conclusion, while malaria is an exceptionally rare cause of Guillain-Barré Syndrome (GBS), it should be considered in patients with recent malaria infection who present with GBS symptoms. Further research is essential to elucidate the molecular mechanisms linking severe malaria with neurological complications such as GBS. This case report underscores the importance of recognizing the potential association between GBS and malaria, aiming to increase awareness among physicians in endemic regions.

CSF

Cerebrospinal Fluid

CBC

Complete Blood Count

GBS

Guillain-Barré Syndrome

Lumbar Puncture

AFI

Acute Febrile Illness

Data availability

On a valid request, the corresponding author will provide access to the datasets that were gathered and used to conduct this article.

Declaration of conflicting interests

No potential conflicts of interest were disclosed by the author(s) with regard to the case report, writing, or publication of this article.

Funding

The case report, authorship, and/or publication of this work were done without any funding.

Ethics approval

The Ethical approval for this report was obtained from College of Medicine and Health Science, Mizan-Tepi University [R.N. HSE/00429/2012]

Informed consent

Before preparing the case report, the patient family provided written informed consent to write the case and be published.

Authors’ Information

MAK is an Assistant Professor, Department of Internal Medicine, School of Medicine, College of Medicine and Health Sciences at Mizan – Tepi University, Ethiopia. MA is a Medical Doctor and specialty certificate in Drug resistant tuberculosis management.

ABT is Assistant Professors of Emergency and Critical care medicine, Department of Emergency and critical care medicine, School of Medicine, College of Medicine and Health Sciences at Mizan – Tepi University, Ethiopia. AB is Medical Doctors and has Specialty Certificate in Emergency and critical care medicine.

MAE Assistant Professors of IM, Department of IM , School of Medicine, College of Medicine and Health Sciences at Mizan – Tepi University, Ethiopia. MA is Medical Doctors and has Specialty Certificate in Internal Medicine.

EPS. Assistant Professors of IM, Department of IM, School of Medicine, College of Medicine and Health Sciences at Mizan – Tepi University, Ethiopia. EP is Medical Doctors and has Specialty Certificate in Internal Medicine.

MTB is Assistant Professors of Emergency and Critical care medicine, Department of Emergency and critical care medicine, School of Medicine, College of Medicine and Health Sciences at Mizan – Tepi University, Ethiopia. MT is Medical Doctors and has Specialty Certificate in Emergency and critical care medicine.

ETM Assistant Professors of IM, Department of IM , School of Medicine, College of Medicine and Health Sciences at Mizan – Tepi University, Ethiopia. ET is Medical Doctors and has Specialty Certificate in Internal Medicine.

Authors’ Contribution

Molla Asnake Kebede, MD

Involved in the conception and design of the study, drafting and revising of the article and final approval of the version to be submitted and also involved in direct management of the patient.

Misikir Alemu Eshetu,MD

Involved in the conception and design of the study, drafting and revising of the article and final approval of the version to be submitted and also involved in direct management of the patient.

Alemayehu Beharu Tekle, MD

Involved in the conception and design of the study, drafting and revising of the article, final approval of the version to be submitted, and involved in direct management of the patient.

Erkihun pawlos Shash, MD

Involved in the study's design, drafting, and revising of the article and final approval of the version to be submitted.

Melaku Tsediew, MD

Involved in the design of the study, drafting and revising of the article, and final approval of the version to be submitted

Elias Tabiet, MD

Involved in the design of the study, drafting and revising of the article and final approval of the version to be submitted

Acknowledgments

The Mizan-Tepi University specifically to the ICU unit staff members and study participants are all sincerely thanked by the authors for their assistance.

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Guillain-Barre Syndrome in a female patient with Falciparum Malaria Infection-a rare case scenario

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Abstract

Background

Clinical presentation

Discussion

Conclusion

Abbreviations

Declarations

Data availability

Declaration of conflicting interests

Funding

Ethics approval

Informed consent

Authors’ Information

Authors’ Contribution

Acknowledgments

References

Additional Declarations

Status:

Version 1