USA: West Nile virus outbreak pattern stymie vaccine work

West Nile virus has been a worry for U.S. pub­lic health depart­ments for more than a decade, but the out­break in 2012 could be on track to be the country’s largest ever. It has already prompted a blitz of warn­ings to avoid virus-infected mos­qui­toes, under­lined with a caveat: There is no vac­cine or treat­ment for West Nile infec­tion. Researchers say the fail­ure is not for lack of trying.

After the first cases were detected 13 years ago in New York City, a burst of money went into thwart­ing the then-mysterious dis­ease. The basic sci­ence has come a long way since then, but mea­sures to pre­vent or treat West Nile infec­tion have stalled. One big rea­son is that the spo­radic nature of out­breaks makes it hard to get enough vol­un­teers for trials.

The peak so far for West Nile was 2003: 9,862 cases and 264 deaths were reported to the Cen­ters for Dis­ease Con­trol and Pre­ven­tion (CDC). In 2012, as of 21 August, CDC had received reports of 1,118 cases and 41 deaths, the high­est count ever by the third week in August 2012. About half the cases have been in Texas, where Dal­las declared a state of emer­gency and began aer­ial spray­ing. Other hot spots are in Mis­sis­sippi, Louisiana, South Dakota, and Okla­homa. Given the up to two-week lag between when peo­ple become infected and when they become ill, cases will likely keep ris­ing through Sep­tem­ber, says Lyle Petersen, direc­tor of CDC’s divi­sion of vector-borne dis­eases in Colorado.

Although the causes of the out­break aren’t clear, many experts sus­pect that hot weather and drought com­bined to spur an explo­sion in Culex mos­qui­toes, the species that spreads West Nile, and a high rate of virus-infected mos­qui­toes. In addi­tion, a mild win­ter helps over­win­ter­ing adult mos­qui­toes sur­vive. Hot tem­per­a­tures spur mos­quito devel­op­ment and allow the virus to repli­cate faster inside mos­qui­toes, notes arbovi­rol­o­gist Laura Kramer of the New York State Depart­ment of Health in Albany. And drought favors Culex mos­qui­toes’ pre­ferred breed­ing habi­tat: pools of water rich in organic mate­r­ial, such as in under­ground drains. Nor­mally, rains flush out such pools. In addi­tion, drought may have forced birds that carry and amplify the virus to move from rural areas to cities to find water, says ento­mol­o­gist William Reisen of the Uni­ver­sity of Cal­i­for­nia, Davis.

Much of the virus’s trans­mis­sion cycle is now well-known: “I think we’ve dis­sected it more than any other mosquito-borne virus that’s been stud­ied,” Kramer says. Researchers also devel­oped fast diag­nos­tic tests for West Nile, includ­ing one that has pro­tected the blood sup­ply. How­ever, efforts to develop a licensed vac­cine stalled. The National Insti­tute of Allergy and Infec­tious Dis­eases (NIAID) poured money into a vac­cine made from a weak­ened back­bone of yel­low fever virus with two genes for coat pro­teins swapped for the West Nile ver­sion of those genes. The vac­cine, devel­oped by Acam­bis in Cam­bridge, Mass­a­chu­setts, made it through a phase II trial that found a sin­gle dose was safe and could gen­er­ate high lev­els of pro­tec­tive anti­bod­ies. “This is a really good vac­cine,” says Thomas Monath, for­mer Acam­bis vice pres­i­dent and now a consultant.

But in 2008, Sanofi Pas­teur bought Acam­bis and sus­pended the West Nile pro­gram. West Nile cases had dropped from 2006 to 2008, and the com­pany decided to focus on other pri­or­i­ties, includ­ing a dengue vac­cine, says Sanofi spokesper­son Susan Watkins. “Unfor­tu­nately we have to pick and choose, and it didn’t make the cut.”

Some researchers say mar­ket uncer­tainty may have been a prob­lem, too. “Who’s going to pay for a vac­cine? It won’t be cheap,” says virol­o­gist Robert Tesh of the Uni­ver­sity of Texas Med­ical Branch in Galve­ston. It might be given only to the elderly, who are most vul­ner­a­ble to severe dis­ease, and per­haps highly exposed groups such as out­door work­ers, says CDC’s Erin Sta­ples. Monath, how­ever, points to new evi­dence sug­gest­ing that West Nile virus can cause kid­ney dam­age in younger peo­ple. A team at Bay­lor Col­lege of Med­i­cine in Hous­ton, Texas, reported August 2012 in PLoS ONE that in a cohort of 139 peo­ple with a mean age of 57 who tested pos­i­tive for West Nile virus, years later 40% had evi­dence of kid­ney dis­ease. “If proven, this cre­ates a com­pletely dif­fer­ent set of pri­or­i­ties for a vac­cine,” Monath says.

Work on treat­ments has been delayed for sim­i­lar rea­sons. Tri­als of three drugs—a mon­o­clonal anti­body, inter­feron, and immunoglobin—were halted in part because researchers couldn’t enroll enough trial vol­un­teers, Sta­ples notes. “It’s going to be dif­fi­cult to do any kind of study with patients in out­break sites when you don’t know when and where it’s going to occur,” says Patri­cia Repik of NIAID.

Yet even if treat­ments were avail­able, they might not be of much help. The virus usu­ally causes only flu­like symp­toms at first; less than 1% of those infected develop seri­ous neu­roin­va­sive dis­ease. By the time patients reach a hos­pi­tal, often with menin­gi­tis or encephali­tis, “the nerve dam­age is already done,” Tesh says. What’s needed, Repik says, is “almost a home test” so peo­ple who get sick could know early on whether they have a West Nile infec­tion. The National Insti­tutes of Health is fund­ing such research as part of $65 mil­lion it will spend in 2012 on West Nile and related diseases.

One frus­tra­tion for West Nile experts is that fund­ing for state labs and CDC’s vector-borne dis­eases divi­sion has dropped off in recent years. Kramer pre­dicts, “This year (2012) may change that.” At the same time, West Nile infec­tions will likely sub­side in 2013 in the cur­rent epi­demic areas because so many birds will have become infected and will be immune to the virus, Reisen says.
(Sci­ence 8/31/2012)