Primary Amoebic Meningoencephalitis (pam)

Introduction:        

Primary Amoebic Meningoencephalitis (PAM) is an infectious, life-threatening disease that produces haemorrhage-necrotizing meningoencephalitis (Martinez, 1977). Naegleria fowleri, a parasite identified as the causative agent of PAM, is an opportunistic free-living protozoan that can be acquired through exposure to contaminated water sources (Anderson, & Jamieson, 1972; Martinez, 1977; Martinez & Visvesvara, 1997). Infections occur when the pathogen enters the host through the nasal route, where they then gain access to the central nervous system (Apley et al., 1970; Culbertson et al., 1959; John, 1982). Since 2012, over 145 cases of PAM have been reported worldwide and the rate of reported incidents has since been demonstrated to increase (Diaz, 2012). Furthermore, from the earliest cases of PAM in 1965 to recent reports in Karachi, Pakistan, in which the majority were young men, it can be observed that this disease primarily infects young people. (Fowler & Carter, 1965; Shakoor et al., 2011). Disturbingly, the mortality rate of this neuropathic disease is 95%, where death generally occurs within 1-2 weeks (Cetin & Blackall, 2012; Herman et al., 2013). The lack of awareness, sanitised water sources, and unavailability successful treatment regimens all contribute to this unnerving fatality rate (Siddiqui & Khan, 2014; Siddiqui, Ali, Cope & Khan, 2016).

Biology of Naegleria fowleri:

Being an amoeboflagellate, N. fowleri can transform into different stages of existence depending on their needs and environment. During its transitory flagellate stage, N. fowleri grows two flagella to allow for movement over large distances in water when nutrients are scarce (Siddiqui et al., 2016; Visvesvara et al., 2007). It also exhibits a non-reproductive, non-feeding resistant cyst stage, where the protist remains dormant under adverse conditions (Siddiqui et al., 2016; Visvesvara et al., 2007). However, during infection, N. fowleri exists in a reproductively-active amoeboid trophozoite stage (Siddiqui et al., 2016; Visvesvara et al., 2007).

Infection:[pic 1]

To cause PAM, N. fowleri migrates through various anatomical parts before reaching the brain. The parasite begins its infiltration through the nasal mucosa, then penetrates the cribriform plate and moves towards the cerebellum via the olfactory bulbs and tracts (Siddiqui & Khan, 2014).  The pathogen then invades the cortex and induces an intense inflammatory reaction (Siddiqui & Khan, 2014). Histological studies have shown evidence of inflammation in both the olfactory bulbs and, especially, the cerebellum (Cermeño et al., 2006).

Symptoms:

The disease tends to cause several symptoms to develop within a week, usually occurring indicatively to its stages (Gupta, Parashar, & Kale, 2015).

Stage 1: Fever, alterations in the sense of taste or smell due to the involvement of the olfactory bulbs, headache, nausea and vomiting (Gupta et al., 2015; John, 1982).

Stage 2: Stiff neck and photophobia (Gupta et al., 2015).

Psychological effects also occur prior to encephalitis, including irrational thoughts, confusion, and irritability (John, 1982). Prior to death, patients usually lapse into seizures, before falling into a coma. The cause of death usually directly relates to the increase in intracranial pressure, leading to the eventual occurrence of brain herniation alongside cranial nerve palsies (Gupta et al., 2015; John, 1982; Siddiqui & Khan, 2014).

Victims and Risks:

Numerous factors, such as one’s lifestyle and location, can increase the risk of infection with N. fowleri. It can be observed through reports of PAM that its victims are usually young people. This trend has been displayed from the first human PAM cases reported, of a 9-year old boy and two 8-year old girls in Australia, to the numerous cases in recent times, including thirteen reports in seventeen months from Pakistan, in which the mean age of its victims was 31 and its youngest victim being only 16 (Fowler & Carter, 1965; Shakoor et al., 2011). N. fowleri amoebae are present in rivers, lakes (natural or man-made), ponds, canals or even poorly treated spas, geothermal springs and swimming pools (Anderson, & Jamieson, 1972; Martinez, 1977; Martinez & Visvesvara, 1997; Siddiqui & Khan, 2014; Siddiqui et al., 2016). Thus, young people with history of swimming or those often exposed to contaminated water sources are not only at risk, but also make up most of PAM cases (Siddiqui & Khan, 2014; Siddiqui et al., 2016). Additionally, in developing countries like Pakistan, where temperature may reach up to 50°C, coupled with constant power cuts as well as poor quality cooling systems, the populace would regularly participate in recreational activities within freshwater sources that are not free of pathogenic microbes. (Siddiqui & Khan, 2014; Siddiqui et al., 2016). Hence, the alarming combination of poor healthcare facilities, lack of awareness and absence of effective medication not only significantly increases the probability of contracting PAM and succumbing to the disease, but also allows the illness to develop undetected, making the existence of N. fowleri a major health risk within communities of developing countries (Siddiqui & Khan, 2014; Siddiqui et al., 2016).

Treatments and Prevention:

PAM has very few treatment regimens, however, the prevention for this disease can be relatively simple. There are only five sufficiently documented cases of survivors who received combination drugs, all of which includes the drug amphotericin B, a drug designed to treat against fungal infections (Hamill, 2013; Siddiqui et al., 2016). However, the dosage of amphotericin B given must be limited due to its toxicity, hence, even when administered, its effectiveness against N. fowleri is very restricted (Hamill, 2013). Despite attempts to improve this drug, while also utilising other drugs in conjunction with amphotericin B, the mortality rate of PAM remains concerningly high. Thus, there is an urgent need to develop effective medication to treat PAM, yet, allow for affordability, as a high portion of PAM victims come from developing countries. Furthermore, the aforementioned factors that increases the risk of being infected by N. fowleri also highlights the essentiality of immediate increase in the awareness of both the public and health professionals alike. Strategies that can prevent PAM, or at least reduce the risk, can include methods as simple as boiling and/or filtering water, or wearing nose clips when participating in water-related activities (Siddiqui & Khan, 2014).