The general recommendation is to ask the reader in the body of the message explicitly to reply to the message to confirm reading it. But even reading it does not always mean one understands it. So even better, do a quiz on the contents of the mail. But still, not getting the confirmation does not mean the message was not read.
But today, I learned of a company which offers the solution to this problem: You have to register with them and get an account (free for 10messages/month, $50 per year for 750messages/month). Then just add .didtheyreadit.com to any email address. This causes the email to be routed through their server where this part of the address is stripped and the message gets an html attachment with a link to an invisible picture (1x1 pixels transparent say) with a unique URL.
The idea is that your email client downloads the picture to display it and they know somebody opened the message in a picture aware browser.
I use pine which is text based and thus does not care about pictures. Thunderbird at least is concerned about my privacy and warns me it didn't download any pictures that were refered to in the message but not contained (note that spammers also use this trick to determine which of the addresses they succed of web pages are actually read and are not directly going into the bit bucket). Still nothing happens. But if I click to download the picture (or use another mail client that is not so careful about my privacy) the sender of the message gets this.
Upshot: If you recieve an email with an attachment that looks like
<div><img src="http://xpostmail.com/b8a6a2cd5cd9ff294ecdf69dbb55d469worker.jpg" nosend="1" name="dtri" width="1" height="1"><link href="http://xpostmail.com/b8a6a2cd5cd9ff294ecdf69dbb55d469.css" hreflang="dtri" rel="stylesheet" type="text/css"></div>
the sender spys on you!