Promising AIDS Vaccine's Failure Leaves Field Reeling

On Tuesday 18 September, AIDS vaccine research suffered one of its most devastating setbacks.

That day, an interim safety analysis that no one expected would reveal anything significant showed that the vaccine widely thought to have the best shot at success had failed in a large human trial. "We were all in shock and devastated," says Peggy Johnston, who heads AIDS vaccine research at the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, which was one of three partners conducting the multicountry trial of the vaccine, made by the pharmaceutical giant Merck.

Three days later, Merck, NIAID, and an academic consortium known as the HIV Vaccine Trials Network (HVTN) announced that the trial, dubbed STEP, had been halted. Started in December 2004, the trial involved 3000 HIV-negative men and women from North and South America, the Caribbean, and Australia who were at high risk of becoming infected.

AIDS researchers around the world were stunned by the trail's results. "This was the first AIDS vaccine clinical trial in history where most people thought they'd at least see something positive," says John Moore, an AIDS researcher at Weill Cornell Medical College in New York City. "It's very dispiriting for the field," says Lawrence Corey, an AIDS researcher at the University of Washington, Seattle, who also heads HVTN. "It will take time to unravel where this leaves us and how we move forward."

Knocked out. Disappointing interim results abruptly ended a Merck vaccine trial that used this recruiting poster. CREDIT: COURTESY OF HVTN

Researchers had pinned their hopes on Merck's vaccine because it uses a novel strategy. Instead of trying to trigger antibodies to HIV, as most other candidates do to some degree, this one relies exclusively on another arm of the immune system that stimulates what are known as killer T cells. HIV has so many mutant types that it's easy for the virus to dodge antibodies. Killer T cells, in contrast, appear to work against a wide array of variants, selectively targeting and destroying cells that the virus has managed to infect. Although only antibodies can actually prevent infections, the hope was that a T-cell vaccine might beat back HIV before it could get a foothold, or at least keep levels of the virus (the viral load) in check.

To trigger the T-cell response, the vaccine uses a modified adenovirus, or cold virus, as a vector to shuttle three HIV genes into the body. But many people have strong immunity to that adenovirus, which theoretically could cripple the vector and render the vaccine ineffective. To assess the magnitude of this problem and increase chances that the vaccine would work, half of the people enrolled in the study had to have low antibody levels against that adenovirus. The interim analysis focused on only those 1500 people, most of whom were men who have sex with men.

In participants who received at least one dose of the vaccine, 24 of the 741 vaccinated people became infected, compared with 21 of the 762 participants who received a dummy shot. More discouraging still, there was virtually no difference in viral loads between the two groups. "I was hopeful we'd see some dampening of viral replication," says Norman Letvin, an AIDS vaccine researcher at Harvard Medical School in Boston, Massachusetts, whose earlier monkey studies with the vaccine did show such a decline.

Letvin and his colleagues vaccinated monkeys and then challenged them with a lab virus, SHIV, which combines HIV with its simian cousin SIV. But when another group later tested the Merck vaccine against a more potent SIV, it failed. To Ronald Desrosiers, head of Harvard's New England Primate Research Center in Southborough, Massachusetts, that failure should have raised more red flags. "Everything protects against SHIVs," says Desrosiers.

Anthony Fauci, NIAID's director, worries that the Merck failure will give the broader T-cell vaccine concept a bad rap. "Clearly this indicates the failure of a product. Whether or not it indicates the failure of a concept, we don't know at this point," Fauci says. NIAID researchers have developed another T-cell vaccine that has more HIV genes and differs in several other key features. A large-scale trial was slated to start this fall but has been delayed pending a more thorough analysis of the STEP results. HVTN has also put on the back burner its plans for a trial of the Merck vaccine in South Africa.

Fauci worries, too, that the failure could have reverberations throughout the pharmaceutical industry, which already is wary of investing in AIDS vaccine research and development. "There's certainly a danger of industry scratching its head and saying before we put substantial resources in, we need more sound scientific data," says Fauci.

Merck, based in Whitehouse Station, New Jersey, would not speculate about the future of its AIDS vaccine program. "The best thing we can contribute to the field overall is a thorough analysis of the data," says Mark Feinberg, the company's vice president of medical affairs. Many intriguing questions remain, he notes, such as what happened in the other 1500 participants, what was the immune responses in the "breakthrough" infection cases, and are there differences in heterosexual transmission (so far, only one woman out of the 1000 volunteers became infected). "It's not like we're not interested in the questions anymore, but it's unclear where the next breakthrough will come from," he says. "And that's not just a question for Merck. It's a question for the entire field."

Hospital privado investe em ciência

Instituições tradicionais estruturam institutos de pesquisa e ensino para captar recursos e melhorar atendimento

Paula Pereira

O Hospital do Coração (HCor) inaugura amanhã uma extensão de sua sede, no bairro do Paraíso, em São Paulo. No lugar de leitos e consultórios, o 11º e o 12º andar do prédio vão abrigar computadores, baias de escritório e prateleiras de livros do mais recente investimento da instituição: um centro de ensino e pesquisa. Seguindo uma tendência internacional, capitaneada por países como Estados Unidos, Inglaterra e Alemanha, hospitais privados brasileiros investem em produção científica, abrindo núcleos próprios e conveniando-se a importantes centros mundiais de saúde.

“Antes, foi a era do tomógrafo e dos equipamentos. Hoje, hospital bom é o que gera conhecimento”, diz Otávio Berwanger, diretor do instituto do HCor, especializado em pesquisas clínicas. “Com essa estrutura, vamos ter capacidade para coordenar projetos internacionais.” Pelo menos dois já estão em andamento, em parceria com uma universidade canadense - um sobre um anticoagulante para pacientes de UTI e outro sobre procedimentos para prevenir problemas cardíacos em cirurgias.

Há três meses, o Beneficência Portuguesa também decidiu reunir pesquisas isoladas do corpo clínico estruturando seu próprio instituto, que deve ser inaugurado em abril. Atualmente, 12 estudos são realizados em convênio com entidades de dez países. No primeiro semestre, o Hospital Alemão Oswaldo Cruz abriu as portas de seu Instituto de Ciências, com orçamento de R$ 5 milhões para estudos em terapias celulares, capacidade individual de resposta a tratamentos e imunologia de tumores. Mais de 30 projetos estão em análise ou em andamento, inclusive testes de medicamentos em conjunto com a indústria farmacêutica.

“Com esse aporte inicial, esperamos alavancar parcerias que potencializem o investimento”, diz o diretor-superintendente, José Henrique do Prado Fay. Simpósios, reuniões científicas, cursos de educação continuada e até lato sensu fazem parte do programa.

Outras instituições tradicionais, como o Israelita Albert Einstein e o Sírio-Libanês, em São Paulo, e o Moinhos de Vento, em Porto Alegre, entraram no ramo há mais tempo. “O hospital não é mais o lugar onde você só vem para ser internado. Vai cuidar do paciente desde a prevenção até a internação”, afirma Roberto Padilha, do núcleo de estudos do Sírio. Com um orçamento de R$ 1 milhão, fora financiamentos de agências de fomento, como a Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp) e o Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), o Instituto de Ensino e Pesquisa do Sírio existe formalmente desde 2003 e tem atualmente 41 protocolos em curso, além de grupos de pesquisa em neurociência, dor, trombose, células-tronco e cardiologia.

De um modo geral, os hospitais já têm algum tipo de pesquisa desenvolvido isoladamente em reuniões científicas ou pequenos grupos. Mas formalizar a estrutura abre portas para financiamentos e parcerias acadêmicas importantes. Foi esse movimento que cresceu nos últimos cinco anos. Alguns centros desenvolvem pesquisa de base, laboratorial, como o Albert Einstein. Mas a maioria se concentra em pesquisa clínica, que investiga a eficácia de medicamentos e protocolos médicos.

INVESTIMENTO PRIVADO

“Na curva de evolução da criação dos comitês de pesquisa, fica claro o investimento do setor privado nos últimos cinco anos”, diz a coordenadora da Comissão Nacional de Ética e Pesquisa (Conep), ligada ao Ministério da Saúde, Gysélle Tannous. Segundo ela, dos 565 comitês de ética e pesquisa existentes hoje no País, cerca de 50% foram criados por entidades particulares - a maioria a partir de 2002.

“Investir em pesquisa leva à sistematização da rotina médica e, conseqüentemente, a melhores resultados”, afirma Ricardo Brentani, diretor-presidente da Fapesp e diretor-presidente do Hospital A.C. Camargo, o Hospital do Câncer, instituição pioneira na associação entre ensino e pesquisa e atendimento, referência na América Latina.

Um estudo da Universidade de Alabama, nos Estados Unidos, comprova o raciocínio de Brentani. Realizada em 2000 com 4,3 mil hospitais divididos entre assistenciais, com algum tipo de ensino e pesquisa e outros com centros estruturados, revelou que a prescrição de medicamentos com benefício comprovado é entre 20% e 25% maior nos que investem em ciência.

Para Gysélle, do Conep, a instituição que aposta nessa tendência se beneficia, principalmente, com a capacitação de pessoal. “Evita que o profissional se acomode e o ajuda a manter uma postura mais reflexiva sobre sua prática.” No final, quem ganha é o paciente, que se sente mais confiante na instituição e nos médicos.

Fidelidade partidária; infidelidade programática

Durante algum tempo fui contra a fidelidade partidária, acho que no início da Nova República. Achava que seria uma ferramenta que impediria o aparecimento de novos partidos e lideranças; que repetiria o velho modelo brasileiro de partidos administrados por uma burocracia (ou por coronéis) centralizada, sem atenção para as diversas características do país.

De lá para cá houve uma multiplicação de partidos, o aparecimento de partidos de aluguéis, e um sistema de presidencialismo de coalizão que abriu espaço para toda sorte de cooptação.

Por isso mesmo, considero importante a votação do STF (Supremo Tribunal Federal) de instituir a fidelidade partidária.

Por outro lado, há outra questão bastante concreta: o Brasil não dispõe mais de partidos. Os partidos que nasceram com a redemocratização envelheceram, perderam a embocadura, não são mais programáticos.

Quando se analisa a quantidade de parlamentares eleitos por votos de legendas, ou a quantidade de suplentes que assume cargos sem ter recebido votos, reforça-se a idéia de que os votos deveriam ser dos partidos. Mas quando se vê esse enorme vácuo político no horizonte, temo que a legislação possa ser um empecilho à formação de novos partidos.

Tomo o meu caso. O PT não me satisfaz. Tinha alguma esperança no PSDB não-fernandista. Hoje esse núcleo não existe mais, com alguns dos melhores quadros se aliando a uma direita raivosa e a um jornalismo de esgoto, achando que é o caminho para o poder.

Jamais vou me filiar a partidos. Mas teria imensa simpatia por um partido não-ideológico, de cunho nacionalista, porém sem xenofobia, que soubesse somar sem preconceitos os diversos ativos que compõem o país hoje em dia: a recuperação do papel do Estado; o fortalecimento das pequenas empresas; a continuidade das políticas sociais atuais, com ampla prioridade para saúde e educação; o fortalecimento da grande empresa nacional, mas dentro de uma estratégia de consolidar cadeias produtivas de pequenas empresas; a defesa intransigente do emprego e da produção nacional; o controle dos fluxos de capitais; os pactos com multinacionais, para atrair investimentos produtivos para o país; a implantação da gestão em todos os níveis de governo.

Um partido como esse conseguiria atrair inúmeros quadros dos demais partidos. Mas qual a chance disso acontecer?

Existe um mundo real e o mundo da política. O mundo real não está muito ligado nessas coisas. Nos ambientes que freqüento, de reuniões empresariais aos botecos, essa discussão não prospera muito. Entre empresários há um sentimento difuso de preconceito em relação ao Lula, muito mais como resultado da campanha de mídia. Em vários setores empresariais – como na construção civil -, Lula é idolatrado. Em outros – especialmente pequena e média empresa e setores exportadores -, é detestado. Em alguns setores sumamente beneficiados, como o mercado financeiro, é suportado. Mas não há ideologia: há interesses.

No mundo da política (e da parcela mais oportunista da mídia) a discussão regrediu cinqüenta anos, para um plano ideológico que não existe mais em nenhuma parte do mundo. De um lado, discutindo Mao, Fidel, a Guerra Fria, pedindo queima de livros e tentando enquadrar o governo Lula em um modelo ideológico que, nem quando o modelo estava vivo, Lula embarcou. Na outra ponta, a desconfiança em relação ao lucro, aos modelos de gestão. Tudo isso compõem um quadro tão antigo quanto a Guerra Fria. Parece que o Almirante Penna Botto saiu do túmulo, e está sapateando no cemitério de braços dados com Prestes.

A fidelidade partidária induzirá os partidos a serem mais programáticos ou, pela falta de alternativas, acirrará esse jogo primário? Essa é a questão.

Luis Nassif

Política e hipocrisia

Na CPI do Mensalão, um dos parlamentares mais críticos e ativos era o deputado federal Eduardo Paes (PSDB-RJ). Batia, questionava, expressava indignação, aparecia.

Esta semana Paes trocou o PSDB pelo PMDB e declarou que, em caso de candidato ao governo do Rio de Janeiro, não abdicará do apoio de Lula. Hipocrisia? Sim. Mas absolutamente usual na política nacional.

Nos seus tempos de oposição, o PT esmerou-se em fazer tempestade em copo d’água para criar crises políticas artificiais ou reais. Como oposição, o PSDB faz o mesmo jogo, a ponto de aliar-se a uma ultra-direita barra –pesada.

Petistas históricos, tucanos históricos estão órfãos. Mas para onde ir?

***

De seu lado, a chamada grande mídia usa politicamente os escândalos, denunciando de maneira seletiva. Exemplo? Denunciou-se o “mensalão” do governo federal. Depois, constatou-se que havia um “mensalão” mineiro.

Em breve será revelado o “mensalão” paulista, mostrando alianças entre o ex-governador do Distrito Federal Joaquim Roriz e o ex-governador paulista Geraldo Alckmin. O mesmo esquema controlou a Nossa Caixa e o BRB, financiou as mesmas ONGs e as mesmas publicações ligadas aos tucanos. E, possivelmente, o mesmo Marco Valério estava por trás do esquema Roriz – já que sua agência era uma das que serviam ao GDF (Governo do Distrito Federal).

É questão de tempo para o Ministério Público completar as investigações.

***

Todo esse estoque de escândalos fica guardado, como produtos em gôndolas de supermercados. Aí o jornal ou a televisão escolhe o alvo que quer atingir, vai na prateleira, tira o produto, desembrulha e transforma em escândalo.

Os atingidos reagem com a indignação dos inocentes; a oposição, com a indignação dos justos. E ambos sabem que tudo não passa de uma enorme marmelada.

***

A tragédia dessa história é que a hipocrisia chegou a tal nível que praticamente transfigurou os partidos políticos. Vinte e cinco anos após a redemocratização, não existem mais partidos políticos programáticos; não existem centros referenciais de pensamento político e econômico; e não existe uma opinião pública que sirva de referência – como ocorreu, bem ou mal, nos anos 80 até meados dos anos 90.

Essa falta de rumo abre espaço para chantagens políticas e jornalísticas de toda espécie. Suponha que, de repente, um presidenciável queira romper com o discurso mercadista e lançar uma nova bandeira.
Imediatamente uma dessas grandes publicações irá até a prateleira, escolherá um escândalo novo ou velho, inédito ou conhecido, e transformará em arma para atingir o indigitado.

Com isso, têm-se hoje presidenciáveis que poderiam estar brandindo um novo discurso, e que quedam inertes, à mercê desse jogo hipócrita.

***

Parte da opinião pública se dá conta dessa hipocrisia. Mas para onde caminhar? Partidos políticos, não mais existem. A perda de rumo é total, entre outras coisas porque estão ocorrendo transformações profundas na sociedade brasileira, que irão resultar inexoravelmente em mudanças.

Que tipo de mudanças? Nem mesmo um oráculo poderá prever.

enviada por Luis Nassif

Influenza — The Goal of Control

Annual administration of inactivated influenza vaccine to older adults has long been recommended by public health authorities.¹ The risks of influenza-related complications, hospitalizations, and deaths increase with age, as does the prevalence of underlying medical conditions. Prospective, randomized, controlled studies have demonstrated that inactivated vaccine is protective against laboratory-confirmed influenza in young adults and, according to much more limited data, in older adults as well.²

Given the demonstrated effectiveness of the vaccine, one might have expected that as the rates of vaccination increased, there would be a corresponding decrease in flu-related hospitalizations and deaths. Instead, the opposite has occurred, with winter hospitalizations and deaths increasing during this period.⁶ There are many possible explanations for this phenomenon, but this observation has called into question previous studies showing large effects on the rates of death from any cause. Many of the previous cohort studies have been limited in that they analyzed only one or two seasons or were conducted at a single site, since reported morbidity due to influenza may vary significantly by season and region.⁷ The study reported by Nichol et al. in this issue of the Journal⁸ addresses many of these concerns and increases our confidence in the benefits of influenza vaccination for older adults.

story

Nothing to Cough At — A 73-year-old man presented to the emergency department with a 4-day history of nonproductive cough that worsened at night

A 73-year-old man presented to the emergency department with a 4-day history of nonproductive cough that worsened at night. He did not have fever, chills, headache, myalgias, rhinorrhea, nasal congestion, sore throat, hemoptysis, chest pain, or dyspnea.

Bordetella pertussis

story

Genomics: The personal side of genomics

Innovations in DNA sequencing and genotyping are opening doors for personal genomics. Nathan Blow explores these technological advances and their implications.

The era of personal genomics is upon us, with advances in technologies such as DNA sequencing and genotyping fuelling the fires. Personal genomics is a story of researchers looking for genetic clues to our most common diseases, of dazzling advances in genetic analysis technology and of lingering questions about how the public will view and use the information.

DNA sequencing is clearly driving much of this revolution in personal genomics. In late May 2007, 454 Life Sciences in Branford, Connecticut, and the Human Genome Sequencing Center at the Baylor College of Medicine in Houston, Texas, made headlines around the world with the announcement that they had sequenced James Watson's entire genome using 454 Life Sciences' next-generation sequencing technology. And just four months later researchers at the J. Craig Venter Institute in Rockville, Maryland, along with collaborators at The Hospital for Sick Children in Toronto, Canada, and the University of California, San Diego, published the first full genome sequence of a single individual — Craig Venter¹. This analysis, though, relied on the traditional approach of Sanger sequencing.

story

Autoimmune disease: Skin deep but complex

Nicole Baumgarth¹ & Charles L. Bevins²

The antimicrobial peptide LL37 is essential for normal immune responses to infection or tissue injury. But in the autoimmune skin disorder psoriasis, LL37 propagates disease by forming complexes with host DNA.

The innate (nonspecific) immune system is responsible for detecting pathogens and inducing effector molecules to coordinate subsequent immune responses and combat infection. Genes encoding the receptors of innate immunity are hard-wired in the host genome, and honed to near perfection by the selective pressures of evolution to respond only to non-self targets. When tolerance (non-responsiveness to self) is broken, this can result in autoimmune disease. On page 564 of this issue, Lande et al.¹ report a costly glitch in the innate immune response that seems to underlie the development of the common autoimmune skin disease psoriasis^∗.

Psoriasis is marked by chronic inflammation and excessive proliferation and turnover of the keratinocyte skin cells, which result in characteristic silvery white scaly patches overlying the inflamed skin². The specific causes of psoriasis are unknown, but environmental triggers — including bacterial skin infections, mild trauma and stress — and strong genetic factors underlie the development of the disease. At a cellular level, an accumulation of inflammatory cells largely consisting of activated T cells and antigen-presenting cells, particularly plasmacytoid dendritic cells (pDCs), precedes other aspects of the disease's pathology. Therefore, psoriasis is currently thought of as an autoimmune inflammatory disorder, but what initiates and perpetuates it has remained enigmatic.

story

Purple Urine

A 76-year-old male nursing home resident with dementia and end-stage renal disease who was undergoing hemodialysis was admitted to the hospital after a syncopal episode that occurred during dialysis. Torsades de pointes was noted on telemetry monitoring. When a urinary catheter was placed, purple urine was drained. The patient had no fever, lower urinary tract symptoms, or leukocytosis. The urinalysis showed a pH of 9.0 and bacteriuria but no hematuria or pyuria. The urine culture showed 10⁵ colony-forming units or more per milliliter for both Pseudomonas aeruginosa and enterococcus species. Over the next 3 days, the urine gradually became yellow and clear, in the absence of antibiotic treatment. Purple discoloration can occur in alkaline urine as a result of the degradation of indoxyl sulfate (indican), a metabolite of dietary tryptophan, into indigo (which is blue) and indirubin (which is red) by bacteria such as Providencia stuartii, Klebsiella pneumoniae, P. aeruginosa, Escherichia coli, and enterococcus species. The clinical course is benign, and the urine typically clears with resolution of the bacteriuria and acidification of the urine. This patient had no further episodes of torsades de pointes and returned to the nursing home in stable condition.

Cases in Vaccine Court — Legal Battles over Vaccines and Autism

Do childhood vaccines cause autism? This scientific question has now become a legal one — perhaps inevitable in our society. Some families with autistic children are pursuing legal channels in an effort to prove that vaccines are responsible for their children's condition. Most of them allege that the cause is the mercury-containing preservative thimerosal, which was formerly used in many vaccines in the United States and elsewhere. Others argue that the culprit is the measles, mumps, and rubella (MMR) vaccine itself or perhaps the vaccine in combination with thimerosal.
Although most experts have concluded that there is no proof of a causal tie between autism and thimerosal or the MMR vaccine, some doctors and scientists, some groups representing families with autistic children, and many parents fervently believe there is a connection. Claimants not only want to prove that the federal government, the Institute of Medicine, vaccine makers, and mainstream science are wrong; they also want money. A child with autism is likely to require extraordinarily expensive services — and to have very limited employment prospects in adulthood. Besides, many parents of autistic children may feel better psychologically if they can blame profit-seeking drug companies for their children's problems.

story

Scientists Are Making Brazil’s Savannah Bloom

By LARRY ROHTER

PLANALTINA, Brazil — Anyone curious to know how Brazil has become what the former secretary of state, Colin L. Powell, calls an “agricultural superpower” — poised to overtake the United States as the world’s leading exporter of foodstuffs — would do well to start here in this busy network of government laboratories.

The New York Times

The sprawling labs and experimental fields are operated by Embrapa, Brazil’s agricultural and livestock research agency, and have become an obligatory stop for any third world leader visiting Brazil.

Although little known in North America, Embrapa has in three decades become a world research leader in tropical agriculture and is moving aggressively into areas like biotechnology and bio-energy.

“Embrapa is a model, not just for the so-called developing world, but for all countries,” said Mark Cackler, manager and acting director of the Agricultural and Rural Development Department of the World Bank. “A key reason that Brazil has done so well with its agricultural economy is that it has invested heavily and intelligently in front-end agricultural research, and Embrapa has been at the forefront of that effort.”

Embrapa owes much of its reputation to its pioneering work here in the cerrado, the vast savannah that stretches for more than 1,000 miles across central Brazil. Written off as useless for centuries, the region has been transformed in less than a generation into Brazil’s grain belt, thanks to the discovery that soils could be made fertile by dousing them with phosphorus and lime, whose optimum mixture was established by Embrapa scientists.

When the annual World Food Prize was awarded last year to two Brazilians affiliated with Embrapa, the citation called the emergence of the cerrado “one of the greatest achievements of agricultural science in the 20th century.”

Embrapa also championed the main crop for the region by developing more than 40 tropical varieties of soybeans, which had been thought of as only a temperate zone crop.

“When I was working in India and Pakistan and the Near East countries in the 1960s and 1970s, nobody thought these soils were ever going to be productive,” Norman Borlaug, an American agronomist who won the Nobel Peace Prize for work that earned him the title “father of the Green Revolution,” said in a telephone interview from Iowa. “But Embrapa was able to put all the pieces together.”

As a result, Brazil is today the world’s top exporter of soybeans and beef and a fast-rising exporter of cotton, three-quarters of which it produces here in the cerrado. Encouraged by that success, Embrapa scientists have turned their attention to wheat. Brazil now imports most of its wheat from nearby countries with temperate climates.

“We think the potential is enormous,” said Roberto Teixeira Alves, general director of the cerrado research center at Embrapa. “We launched two new varieties of wheat with good yields just last year, and believe there is also a strong possibility of adapting barley to the region.”

story

Deep Questions in the Tree of Life

Patrick J. Keeling^*
A genome sequence might provide answers to major questions about the biology and evolutionary history of an organism. Alternatively, it might reveal more problems than solutions, and its true value then lies in identifying what questions to ask. Perhaps the most interesting genomes do both: They are a panacea and a Pandora's box. On page 1921 in this issue, Morrison et al. (1) describe such a genome from the diplomonad protist Giardia lamblia, a human intestinal parasite. The compact Giardia genome is replete with information ranging from the simplicity of its molecular systems to how the parasite interacts with its environment. However, the evolutionary history of Giardia is not so clearly written in the genome, reigniting a smoldering debate about the origin of Giardia and its relationship to other eukaryotes.

story

Vaccine-Related Polio Outbreak in Nigeria Raises Concerns

Leslie Roberts

Northern Nigeria has been hit by one of the largest known outbreaks of poliomyelitis caused by the live polio vaccine itself. The ongoing outbreak could be a serious setback for the global polio eradication campaign: It is occurring in a region where rumors about vaccine safety derailed vaccination efforts several years ago.

Experts with the Global Polio Eradication Initiative emphasize that the widely used trivalent oral polio vaccine (OPV) is safe. But the low immunization rates in northern Nigeria have created the conditions for the attenuated vaccine virus to regain its virulence and trigger an outbreak.

Detected in September 2006, the outbreak of vaccine-derived poliovirus (VDPV) type 2 was immediately reported to the World Health Organization and Nigerian health officials. But the information is just now being released publicly--in the 28 September Morbidity and Mortality Weekly Report and WHO's Weekly Epidemiological Record--a delay that has caused some consternation in the polio community. Officials say they were worried that the news, if misconstrued, could again disrupt polio vaccination efforts in Nigeria.

"There were legitimate concerns that anti-polio vaccination rumors would be rekindled by an incomplete explanation of the cause of the VDPV outbreak," says Olen Kew, who has led efforts to analyze the outbreak from the U.S. Centers for Disease Control and Prevention in Atlanta, Georgia.

Double whammy. Northern Nigeria is battling wild and vaccine-derived poliovirus. CREDIT: JEAN-MARC GIBOUX

Several polio experts told Science that although they understand how sensitive the situation is, they disagree with the decision to keep quiet. "I am troubled that the information hasn't come out, absolutely," says Donald A. Henderson of the University of Pittsburgh Center for Biosecurity in Baltimore, Maryland. Henderson says details of each outbreak are essential if scientists are to understand just how risky these vaccine-derived strains are.

So far, there are 69 confirmed cases of paralysis, and more suspected, caused by VDPV in nine northern Nigeria states, says Kew. The case count seems certain to rise. About half the cases have occurred around Kano, a largely Muslim state where anti-Western sentiment and rumors that the vaccine caused sterility or AIDS led several states to halt polio vaccination in 2003. After repeated demonstrations of the vaccine's safety and considerable behind-the-scenes diplomacy, vaccinations resumed about a year later, but the damage had already been done.

By the end of 2004, the number of polio cases in Nigeria had doubled to about 800, and in 2006 it soared to more than 1100. Wild virus from Nigeria reinfected some 20 other countries, leading to a spike in global cases. It was a huge setback to the Global Polio Eradication Initiative, which estimates that the world spent an additional $500 million to contain the damage. Only recently have global cases dropped back to near preboycott levels.

Although Nigeria has since made considerable progress, wild poliovirus, both type 1 and type 3, is still circulating in the north, and vaccine coverage there remains low. In 2006, between 6% and 30% of children in the north had never received a single dose of OPV.

Those are exactly the conditions that render an area susceptible to outbreaks of vaccinederived virus. Since the 1960s, scientists have known that attenuated viruses can in rare instances mutate and regain virulence, but it was only in 2000, with an outbreak in Hispaniola, that they realized VDPVs could spread disease from person to person.

The current outbreak came to light when a technician at the CDC polio lab noticed a preponderance of type 2 virus in the isolates sent in from northern Nigeria. That instantly raised suspicion, Kew says, because wild type 2 poliovirus has been eradicated globally. That meant the only possible source was the trivalent vaccine, which had been used in Nigeria in preboycott campaigns. Since Nigeria resumed vaccinations in 2004, says Kew, it had "quite properly" been using the more effective monovalent vaccines against wild types 1 and 3 in its campaigns. Genetic analysis quickly confirmed the source; it also suggests that several VDPVs emerged independently in 2005 and 2006, multiple times.

In earlier outbreaks, circulating VDPVs have been relatively easy to stamp out, but this one has persisted despite four campaigns with trivalent OPV in the past year. "We suspect it is simply because the coverage was not adequate; we don't believe there is anything exceptional about this virus," says Kew. As evidence, he notes that two VDPV strains jumped from Nigeria to Niger, where routine vaccination is almost 90%. Both "barely made it 5 kilometers before they dead-ended," he says.

Polio expert Oyewale Tomori, vice chancellor of Redeemer's University near Lagos and chair of Nigeria's expert advisory committee for polio eradication, says he has been urging officials to go public. He worries that secrecy might fuel suspicions about vaccine safety instead of reinforcing the need to intensify immunizations in Nigeria.

Semana Nacional de Ciência e Tecnologia

Por Neo Tupi

Nassif, ajude a divulgar:

Hoje começa a Semana Nacional de Ciência e Tecnologia.

São mostras e feiras de ciências em diversas cidades do Brasil, desde centros de pesquisa até tendas em praças públicas.

É para as pessoas levarem as crianças (de qualquer idade), e despertar o instinto de professor Pardal (ou o Franjinha do Maurício de Souza) dentro de cada um.

Porquê o Brasil tem bons jogadores e jogadoras de futebol, de vôlei e de basquete? Porque são esportes muito divulgados e praticados nas escolas, nos clubes, nos campinhos dos terrenos baldios e quadras de bairros. As crianças com talento para esportes descobrem sua vocação ali, e alguns despontam seguindo carreira.

O mesmo acontece com crianças e jovens quando tem contato com a ciência, em feiras e mostras. Aqueles que tem vocação, ao tomarem contato, descobrem um mundo novo, divertido e mágico ali, e muitos deles vão trilhar o caminho do estudo e trabalhar com ciência e tecnologia, encontrando soluções para os desafios do mundo futuro.

Para saber dos locais das mostras em cada cidade consulte http://semanact.mct.gov.br

Em tempo: a semana nacional foi criada em 2004 pelo MCT. Isso desmistifica um pouco o preconceito de que o atual presidente não incentiva o saber.