His body wasted from AIDS, Fred Muzaya sat up in his bed on a January morning at Mulago Hospital in Kampala, Uganda, and faintly smiled at a doctor he couldn't see.
A former taxi driver, Muzaya, 26, may have been infected with HIV several years ago, perhaps more. But it was only months ago that he finally went to a doctor — when a pain in his head that had started several weeks earlier became too much to bear.
The culprit: cryptococcal meningitis, a fungal disease of the brain and spinal cord.
A so-called opportunistic infection, crypto is a threat primarily to those with HIV who lack access to the antiretroviral therapy that can keep the virus in check. A healthy immune system can fight off crypto with ease. But in Muzaya, who had never taken the drugs, the fungus had spread unchecked, impairing a process critical to survival: reabsorption by the brain of cerebrospinal fluid.
Over time, the fluid, which is continuously produced, built up in Muzaya's skull, slowly squeezing his brain. Bedridden by an unrelenting headache, he became disoriented and, soon, his hearing and eyesight began to fail. By the time he arrived at Mulago, Muzaya was completely blind and nearly deaf.
Gently, Dr. Reuben Kiggundu, an infectious diseases specialist, took Muzaya's head in both hands and, as though calling out to a miner trapped below ground, spoke directly into one ear.
"Can you hear me, Fred?" he asked loudly in Luganda, the language spoken most widely here.
Moments later, and loudly enough for all on the ward to hear, Muzaya called out: "Doctor! I have no complaints!" Then he curled up in a fetal position for the procedure he needs nearly every day: a lumbar puncture, or spinal tap, to relieve the pressure in his skull.
Muzaya lay still while Kiggundu moved a gloved thumb over his lowermost vertebrae and slid a needle through the tissue in between. As clear fluid rushed through the syringe and into a vial, Muzaya let out a sigh.
"The relief is immediate," Kiggundu said. "They feel so much better after we do the LP. But tomorrow he'll probably need another."
AIDS, we often hear, is in retreat. According to the latest report by Unaids, the United Nations' HIV-fighting agency, more than 15 million people worldwide are taking antiretrovirals. New infections have fallen by 35 percent since 2000; AIDS deaths are down sharply. If progress continues, say officials, the epidemic could soon be brought to an end.
And, yet, to clinicians across the developing world, cases like Muzaya's are frustratingly common. They're difficult to manage and most often fatal, and they point to what some experts say is a blind spot in efforts to end the epidemic: a persistent failure to catch the many patients who, for any number of reasons, either fall through the cracks along the "cascade of care" — the journey from an HIV diagnosis to suppression of the virus – or, like Muzaya, come in for testing only after they've fallen ill.
Indeed, for all of the progress in expanding access to care, fewer than half of the 37 million people infected with HIV worldwide have been reached with antiretrovirals. And while retention in HIV care has greatly improved, roughly a quarter of adult patients in Africa are "lost to follow-up" — they have stopped taking the drugs and are unreachable — or deceased within two years of starting treatment, a product, in large part, of the stigma still firmly attached to a positive status.
That's one reason crypto remains a menace. Globally, the disease claims an estimated 300,000 lives every year, roughly 20 percent of all AIDS-related deaths. In fact, according to the U.S. Centers for Disease Control and Prevention, crypto annually kills nearly as many people in sub-Saharan Africa as tuberculosis — and more in a month, every month, than the worst Ebola outbreak on record.
Yet experts say it may also be the easiest to tackle, especially with the advent of a new rapid test called the Cryptococcal Antigen Lateral Flow Assay, or CrAg LFA.
"The key is to identify those patients who are infected before they ever get sick," says David Meya, a senior lecturer in infectious diseases at Uganda's Makerere University and the principal investigator on a study that looks at using the new test in Uganda.
Developed by Immuno Mycologics, a.k.a. Immy, a family-run company in Norman, Okla., the CrAg LFA is designed to work in settings where crypto is most prevalent — where doctors are scarce and electricity is unreliable. Unlike other diagnostic tools, the CrAg LFA requires no refrigeration, laboratory infrastructure or skilled technicians. Similar to a pregnancy test, it uses a dipstick and a test tube to detect the presence of an antigen (a substance that is highly predictive of the development of cryptococcal disease) in cerebrospinal fluid, blood or urine. It's easy to use and interpret — one line is negative, two is positive — and it's faster and more accurate than anything on the market.
But the greatest boon is that the CrAg LFA can detect a cryptococcal infection weeks to months before a person develops symptoms. That makes it possible for patients to avoid not only the awful symptoms but also the long-term, labor-intensive hospitalization.
"That is the key driver of costs," says Tom Chiller, deputy chief of the CDC's Mycotic Diseases branch. This CDC group has been working with ministries of health in Africa and Asia to design screening programs around the CrAg LFA. "We know that if countries screen and immediately treat those who test positive, they're going to save lives and save money." Multiple studies have borne that out.
Care for a single crypto patient in Kampala, for example, typically runs in excess of $400. By comparison, the estimated cost of saving one life by screening patients with the CrAg LFA and treating them with an antifungal drug called fluconazole, comes to less than $40.
In late 2009, Jeff Klausner, then chief of HIV/TB care and treatment for the CDC-South Africa, called Chiller about startling data he'd seen on the fungal killer. "Tom said, 'We've been working on this for five years and no one from the AIDS programs have reached out to us,' " remembers Klausner. "I said, 'Well, here I am.'" Chiller told Klausner about the CrAg LFA, then under evaluation, "and I was like, boom. This is a home run."
Months later, Klausner briefed CDC director Dr. Tom Frieden on the situation, "and he got it very quickly," he says. "He called it 'one of our winnable battles.' He said 'OK, this is feasible, it's cost-effective, let's figure out how to scale it up.'"
Since then, though, momentum has stalled.
To date, 16 countries have included CrAg screening in their national guidelines and drawn up plans for a program. But few have actually procured the $2 test or begun to use it in routine HIV care. And only one, Rwanda, has rolled out screening at the national level.
"Policymakers think if they just focus on HIV testing and treatment, crypto will no longer be an issue," says Klausner. "And I think that's somewhat based on denial that the systems in place are not working well enough."
Donors, too, he says, have looked the other way, focusing instead on "upstream" interventions that prevent new infections — like the development of an HIV vaccine. "Maybe they don't understand the problem, maybe they don't see the cost-effectiveness of it, I don't know," he says, "but they've dropped the ball on this."
"Even people within the field will tell you that crypto is going to go away," adds Angela Loyse, an infectious diseases researcher at St. George's University of London. "I've been hearing that since I started out in 2006. How long can you say it? To my mind, it's just not acceptable."
But Chiller is optimistic that a champion will step up.
"We think countries can sustain screening for a relatively small amount of funding," he says. "They just need the start-up money — $5 million to get it going, get people trained, get the supply chains in place. An organization that's willing to kick-start CrAg screening in these countries could make a really big difference."
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