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Abstract

Infections by herpes simplex virus (HSV) cannot yet be eliminated, but the severity of the disease can be reduced. Two newer drugs with established efficacy for such infections, famciclovir and valacyclovir, were tested in a mouse eye model of HSV infection. Both drugs significantly reduced mortality and titers of virus shed from the eyes of mice infected with an otherwise lethal dose of HSV type 1 (HSV-1). Similar titers of HSV-1 were found in the eyes, ganglia, and brains of treated animals. Although valacyclovir reduced the latent viral DNA load better in these studies than did famciclovir, rates of reactivation by explantation and UV exposure were the same. Thus, in this study, famciclovir and valacyclovir were equally effective in limiting the virulence and spread of HSV-1, despite their biochemical and pharmacologic differences.

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Herpes simplex virus (HSV) types 1 and 2 are important human pathogens that cause orofacial and genital lesions [ 1 ]. During the initial infection, HSV infects neurons, where it remains in a latent state until reactivated by stimuli such as heat and UV light [ 2 , 3 ]. In vivo reactivation of HSV depends on multiple factors, such as the anatomic site of infection [ 4 ], the host's immune status [ 5–7 ], and the quantity of latent viral DNA [ 8 ].

Currently, there is no vaccine or cure for HSV infections; however, treatments are available that diminish the severity of the disease. Valacyclovir and famciclovir, the oral forms of acyclovir and penciclovir, respectively, are guanine analogues that inhibit HSV replication at the level of DNA synthesis [ 9–16 ]. Acyclovir has been the standard for treating herpes infections; however, because of its poor bioavailability (15%–20% vs. 55% for valacyclovir and 75% for famciclovir), it was prudent to develop new compounds. Following their absorption, valacyclovir and famciclovir are rapidly and efficiently metabolized by host enzymes to acyclovir and penciclovir, respectively.

Both acyclovir and penciclovir enter infected and uninfected cells but require viral thymidine kinase for activity [ 9 , 14 , 15 ]. Previous reports showed that penciclovir has a higher affinity than acyclovir for the viral thymidine kinase, a faster rate of phosphorylation, and a longer intracellular half-life [ 10 , 11 ]; however, penciclovir has a lower affinity than acyclovir for the HSV DNA polymerase. The end result is that the penciclovir prodrug, famciclovir, which is effective in humans at doses similar to those for acyclovir, can be given less often. The higher acyclovir blood levels effected by valacyclovir achieve the same end result of reduced dosage frequency. Given these modest differences between valacyclovir and famciclovir, it is noteworthy that a series of animal studies suggested that famciclovir is better than valacyclovir in terminating ganglionic HSV infection and thereby limits subsequent reactivation [ 17–20 ].

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When you're talking about a nation of some 17,000 islands, you need to be realistic in what you are trying to achieve. Simply put, we'd say a reasonable timeline to travel from Pulau Weh in the west to Kupang in the east, with a few side trips here and there, would require a minimum of six months. Minimum.

Explore the secret gilis... Photo: Stuart McDonald

Two weeks should be about your baseline for any one of the main islands—and while that will be sufficient for you to knock off some of the main attractions at a comfortable pace, a month is a better spread. A month in Sumatra, a month in Bali, a month in Lombok, a month in Sumbawa, a month in Flores ... You did put your leave form in right?

Trying to cover too much territory in too little time does not work in Indonesia . If you have limited time (say two weeks) make judicious use of domestic flights and be selective in where you go. Jakarta, Yogyakarta, Ubud and Gili T will work in two weeks assuming you're flying the longer legs—we wouldn't advise trying to fit in more.

does not work in Indonesia

If you are planning a longer stay, it pays to familiarise yourself with Indonesia’s visa rules . They change occasionally and some rules are enforced haphazardly, complicating what should be a simple process.

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Outside of Bali, Indonesia is an affordable country and budget travellers comfortable in simple accommodation, eating street food, not drinking too much alcohol, travelling using cheap transport and steering clear of heavily touristed (and so more expensive) destinations, can get by on around US$20 a day. Alcohol is expensive by regional standards, so if you like four or five sundowners rather than one, you'll need to factor that into your budget.

Fake or real? Photo: Stuart McDonald

Most independent travellers tend to spend a little more. That air-con room is tempting, as is the pool and WiFi, real latte and occasional VIP bus or short domestic flight. All these conspire to push daily budgets up to around a more comfortable US$30-40 per day.

push daily budgets up

If your tastes veer more towards the luxurious, then Indonesia does offer terrific value for accommodation in the US$100-$200 mark, especially in Bali. Food and entertainment costs can potentially increase accordingly.

Indonesia does offer terrific value
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So much to read, so little time. Photo: Stuart McDonald

In terms of international acclaim, Kurniawan picks up the mantle from Pramoedya Ananta Toer, the Southeast Asian writer probably the nearest to win a Nobel prize for literature. Pramoedya’s Buru Quartet cover Indonesian’s political awakening under Dutch colonial rule. At the least, read the first novel of the series of four, This Earth of Mankind , an unblinking examination of colonialism, racism and sexism, woven through a colourful coming-of-age tale.

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