**4. Conclusions**

Regarding encephalitis caused by FLA, it is important to mention that because most of them are ultimately fatal, diagnosis of these infections is often made at autopsy, even in developed countries where sophisticated diagnostic facilities are readily available. However, in Sub-Saharan Africa and Southeast Asia, where HIV/AIDS rates are increasing, it is quite possible that a large number of cases have gone undetected. A similar case occurs in South America, where skin infections due to *B. mandrillaris* are a common episode in countries like Peru but the lack of diagnostic and treatment facilities in most areas have caused that most of these cases have been unnoticed as well.

This due to a number of reasons: (1) lack of expertise to identify these pathogenic amoebae; (2) cultural methods and expense that prevent autopsies; and (3) an abundance of more prominent diseases such as HIV/AIDS, tuberculosis and malaria that consume national and international resources. Therefore, the actual incidence of the encephalitis caused by FLA is not really known although it seems that these pathogenic amoebae are emerging as causative agents of encephalitis worldwide.

### **5. References**

336 Non-Flavivirus Encephalitis

*Balamuthia mandrillaris (BAE)* 

Found in soil and water; preventive measures not feasible

Pentamidine, azithromycin, fluconazole, flucytosine

Poor; diagnosis is

postmortem−three patients have survived

often

*Sappinia spp.* 

Azithromycin, pentamidine, itraconazole, flucytosine

Insufficient data

Insufficient data; organism found in soil; preventive measures not feasible

*Acanthamoeba (AGE)* 

Widespread in soil and water; in hospital setting, monitoring of water supply, ventilators, air conditioning units

Pentamidine, azole compounds, flucytosine, sulfadiazine

Poor; diagnosis is

postmortem−only a few patients have survived

Table 1. Characteristics of FLA as causal agents of encephalitis (adapted from Visvesvara et

Recently, the application of siRNA in *Acanthamoeba* species (Lorenzo-Morales et al., 2005; 2008; 2010) has opened a novel approach for the progress of future therapies based on siRNAs alone or in combination with chemical compounds. Also the use of RNAi moleculaes could be very powerful for the identification of novel drug targets and metabolic pathways in these pathogens that could be exploited for the development of new therapeutic agents. Recently, RNAi methodology has been successfully use in *Naegleria fowleri* (Jung et al., 2008) resulting in a reduced pathogenicity of the RNAi-treated amoebae. Therefore, RNAi molecules are currently presenting as very powerful tools that are waiting

Regarding encephalitis caused by FLA, it is important to mention that because most of them are ultimately fatal, diagnosis of these infections is often made at autopsy, even in developed countries where sophisticated diagnostic facilities are readily available. However, in Sub-Saharan Africa and Southeast Asia, where HIV/AIDS rates are increasing, it is quite possible that a large number of cases have gone undetected. A similar case occurs in South America, where skin infections due to *B. mandrillaris* are a common episode in countries like Peru but the lack of diagnostic and treatment facilities in most areas have

This due to a number of reasons: (1) lack of expertise to identify these pathogenic amoebae; (2) cultural methods and expense that prevent autopsies; and (3) an abundance of more prominent diseases such as HIV/AIDS, tuberculosis and malaria that consume national and international resources. Therefore, the actual incidence of the encephalitis caused by FLA is not really known although it seems that these pathogenic amoebae are emerging as

to be fully exploited in the development of new therapies against pathogenic FLA.

caused that most of these cases have been unnoticed as well.

causative agents of encephalitis worldwide.

often

*Naegleria fowleri* 

Public health monitoring of warm, freshwater recreational

*(PAM)* 

sites

**3.5 Novel therapeutic approaches** 

Intrathecal amphotericin B, miconazole

Fair if diagnosed early (within days); otherwise poor−a few patients have survived

*Prevention* 

*Current therapy* 

*Prognosis* 

al., 2007).

**4. Conclusions** 


**Part 4** 

**Multicellular Pathogens** 


**Part 4** 

**Multicellular Pathogens** 

338 Non-Flavivirus Encephalitis

Martínez DY, Seas C, Bravo F, Legua P, Ramos C, Cabello AM, Gotuzzo E. (2010). Successful

Matin A, Siddiqui R, Jayasekera S, Khan NA. (2008).Increasing importance of Balamuthia mandrillaris. Clinical Microbiology Reviews. 2008 Jul;21(3):435-48. Review.

Patel DV, Rayner S, McGhee CN (2010).Resurgence of Acanthamoeba keratitis in Auckland,

Petry F, Torzewski M, Bohl J, et al. (2006). Early diagnosis of Acanthamoeba infection during

Qvarnstrom Y, da Silva AJ, Schuster FL, Gelman BB, Visvesvara GS. (2009). Molecular

Seijo Martinez M, Gonzalez-Mediero G, Santiago P, Rodriguez De Lope A, Diz J, Conde C,

Shirwadkar CG, Samant R, Sankhe M, Deshpande R, Yagi S, Schuster FL, Sriram R,

Tu EY and Joslin CE (2010). Recent outbreaks of atypical contact lens-related keratitis: what

Verani JR, Lorick SA, Yoder JS, Beach MJ, et al. (2009). National outbreak of Acanthamoeba

Visvesvara GS and Maguire JH (2006) Pathogenic and opportunistic free-living amebas.

Visvesvara GS, Moura H and Schuster F L (2007), Pathogenic and opportunistic free-living

Sappinia diploidea. FEMS Immunology and Medical Microbiology, 50:1–26. Visvesvara GS, Sriram R, Qvarnstrom Y, Bandyopadhyay K, Da Silva AJ, Pieniazek NJ,

Walochnik J, Wylezich C, Michel R. (2010)The genus Sappinia: history, phylogeny and

medical relevance. Experimental Parasitology. 126(1):4-13.

Page, F.C. (1988) A new key to freshwater and soil gymnamoebae. FBA NERC. P26.

Journal of Infectious Diseases. Apr 15;199(8):1139-42.

India. Emerging Infectious Diseases. 2006 Jun;12(6):984-6.

57(Pt 11):1399-404.

Ophthalmology 38(1):15-20.

Microbiology. 44(5):1903-4.

Infectious Diseases. 15(8):1236-42.

eds), pp. 1114–1125. Churchill Livingstone.

38(10):3892-5.

Aug;56(4):357-66.

608.e2.

treatment of Balamuthia mandrillaris amoebic infection with extensive neurological and cutaneous involvement. Clinical Infectious Diseases. 2010 Jul 15;51(2):e7-11. Martín-Navarro CM, Lorenzo-Morales J, Cabrera-Serra MG, Rancel F, Coronado-Alvarez

NM, Piñero JE, Valladares B. (2008). The potential pathogenicity of chlorhexidinesensitive Acanthamoeba strains isolated from contact lens cases from asymptomatic individuals in Tenerife, Canary Islands, Spain. Journal of Medical Microbiology.

New Zealand: a 7-year review of presentation and outcomes. Clinical Experimental

routine cytological examination of cerebrospinal fluid. Journal of Clinical

confirmation of Sappinia pedata as a causative agent of amoebic encephalitis.

Visvesvara GS.(2000).Granulomatous amebic encephalitis in a patient with AIDS: isolation of acanthamoeba sp. Group II from brain tissue and successful treatment with sulfadiazine and fluconazole. Journal of Clinical Microbiology. Oct;

Visvesvara GS. (2006). Acanthamoeba encephalitis in patient with systemic lupus,

have we learned?. American Journal of Ophthalmology. 2010 Nov;150(5):602-

keratitis associated with use of a contact lens solution, United States. Emerging

Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. Tropical Infectious Diseases, Vol. 2 (GuerrantRL, WalkerDH & WellerPF,

amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and

Cabral GA. (2009). Paravahlkampfia francinae n. sp. masquerading as an agent of primary amoebic meningoencephalitis. Journal of Eukaryotic Microbiology. Jul-

**15** 

*Gabon* 

Jean Paul Akue

*Franceville (CIRMF),* 

**Encephalitis Due to** *Loa loa*

*Loa loa* encephalitis is becoming an important public health problem, as it impedes the use of some important drugs (ivermectin and DEC) for mass control of filarial disease in parts of West Africa where onchocerciasis is endemic. Loa encephalitis may occur either spontaneously or following chemotherapy targeting *Loa loa*. Although *Loa loa* is restricted to the West African rain forest block, imported cases are described throughout the world, due to intense economic, cultural and touristic population exchanges. The most common clinical features of loiaisis are swelling angioedema (calabar oedema) and ocular passage of the adult worm under the conjunctiva (eye worm). *Loa loa* disease may be particularly severe in expatriates (Nutman et al., 1986). *Loa loa* may cause a localized or systemic disease with involvement of deep organs including the kidney and heart. Only one-third of infected individuals have microfilariae in peripheral blood, leading to an underestimation of the prevalence of this infection. Most expatriates with loiasis have the adult worm but are amicrofilaremic (Churchill et al., 1996). The heterogeneous clinical expression of loisais encephalopathy calls for greater awareness among scientist and medical practitioners

*Loa loa* is a filarial worm restricted to West Africa (Figure 1), from Guinea in the north through Benin to Uganda in the East, Gabon, Cameroun and Nigeria in the west, and Angola in the South. Parts of Cameroun, Gabon, Nigeria, Congo Brazzaville and Congo Kinshasa (DRC) are hyperendemic. Common clinical signs include eye worm and calabar swelling. *Loa loa* adults produce microfilariae that are released into the peripheral blood. They reach their maximal concentration in peripheral blood during daytime (diurnal periodicity). This larval stage of *Loa loa* is the likely etiologic agent of encephalitis during loiasis. The parasite was first described in 1770 (Mongin, 1770) in the eye of a servant in the island of St Domingue. Only few autochtonous case of loaisis has been reported outside of Africa, in India (Barua et al., 2005; Kethan, 2007), although *Loa loa* can develop successfully in *Chrysops atlanticus*, which is widespread in Louisiana and Mississippi (Orihel & Lowrie, 1975). *Loa loa* is thought to infect 13 million individuals living in endemic zones (Fain, 1978), as well as individuals visiting these areas (Varhaug,2005; Carbonez et al.,2002; Hee-Yoon et

**1. Introduction** 

worldwide.

**2. The pathogen:** *Loa loa*

*International Center For Medical Research* 
