The last blog post on malaria in The Audiology Condition described preventive approaches–mainly “chemoprophylactic” medication regimens– used to avoid contracting malaria in countries where the disease is endemic. There are five drugs in the preventive regime. None are effective in all endemic countries, all have side effects that include hearing and balance disorders.
Today’s post looks at all drugs in the anti-malarial medicine cabinet, along with their effects on the auditory/vestibular systems.
Anti-malarial Drugs — A WHO Nightmare
Table 1 and Figure 1 show the handful of drugs available to combat malaria in its “regular” and severe forms. I’ve done my best to ferret out the applications of the drugs, their effectiveness, and the possible effects on hearing and balance but investigating this disease and its treatments is a lot like going down the Alice in Wonderland rabbit hole.
Most drug regimes are relatively new — post Viet Nam War era but waning fast in effectiveness as malarial parasites develop resistance in different geographic regions (Figure 1). The single drug treatment that hangs tough continues to be quinine, the oldest treatment of all. It remains relatively effective (Figure 1) over 400 years of use, dating back to its discovery during the Spanish conquest of the New World.
The World Health Organization (WHO) is constantly monitoring endemic countries, regions, cities, remote villages and revising its recommendation for drug prevention and treatment regimes. Drug resistance pops in one place, counterfeit drugs pop up there and other locations, different types of malaria are treatable by different drugs, pregnancy malaria poses special drug-treatment problems… the list goes on and is absolutely bewildering.
In the midst of malaria’s rapid development of resistance to the new, “first line” drugs, quinine remains an effective treatment. Quinine is not a first line drug because the side effects from even therapeutic doses are reliable and severe. The constellation of symptoms is so predictable that it’s gained its own clinical name — cinchonism. Even mild cinchonism includes high frequency hearing loss, tinnitus and dizziness which are likely to disappear post-treatment.
Table 1. Antimalarial drug armamentarium, applications,
effects on hearing and balance.
|Antimalarial Drugs||First or Second Line Treatment||Auditory/Vestibular Effects|
|mefloquine||2nd line: P. falciparum and P. vivax||Hearing Loss, tinnitus, dizziness, loss of balance|
|chloroquine (Lariam®)||1st line: P. vivax and P. ovale||Hearing loss, tinnitus, dizziness|
|primaquine||Dizziness; hearing loss with chronic overdose|
|quinine & quinidine||1st line: 1st trimester of pregnancy malaria||Cinchonism with therapeutic doses: hearing loss, deafness, tinnitus, vertigo, dizziness. Reversible except in severe cinchonism.|
|clindamycin[ii]||Transient tinnitus (93.7%) in combined treatment with quinine|
|artemisinin-based combination therapies (ACT)[iii]artesunate[iv]artemether-lumefantrine (Coartem®)[v]||First line: P. falciparum||hearing loss above 500Hz in uncomplicated malarianeurotoxic potential in brainstem auditory pathways but no evidence of auditory effects in small human study|
[iii]Always used in combination with other antimalarial to avoid developing drug resistance (e.g., artesunate+ mefloquine or amodiaquine).
[iv]Not licensed for use in the United States. CDC makes it available.
[v] FDA approved in 2009 for P. falciparum
The Audiology Connection
With possible exceptions for aminoglycosides (e.g., doxycycline, clindamycin) in the multidrug treatments shown in Table 1, there is little understanding of how the antimalarial drugs produce ototoxicity. Reports of hearing loss are conflicting for the newest, first-line treatment drug regime (artemisinin in combination), possibly due to combining it with aminoglycosides. Even 400-year quinine remains a mystery when it comes to ototoxicity, despite it’s reliable effect on the auditory/vestibular system. That is the subject of next post in this series.
In the meantime, Table 1 signals a need for Audiologists to increase their awareness of malaria characteristics (exposure, onset time, symptoms), malaria treatment (preventive and curative), adverse effects on hearing and balance, and the growing number of returning travelers exposed to malaria in endemic countries.
Pre- and post-travel/treatment audiometry is in order for those journeying to countries where malaria is endemic. For those who return with malaria or develop flu-like symptoms after returning, repeat and possibly serial audiometry is in order, in close communication with patient and physician or hospital staff.