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While the evidence linking Zika virus infection and
While the evidence linking Zika virus infection and GBS in adults and separately between microcephaly and other neurological conditions in the fetuses of pregnant women is strong and growing, many key research and public health questions need to be addressed through comprehensive epidemiological studies to better understand the extent of Zika virus infection and the diseases Zika virus causes in humans and their offspring. WHO and PAHO have convened several meetings to discuss research needs and questions during which partners, diverse organisations, and institutions have identified research gaps and explicitly established research priorities to tackle key public health questions raised by this outbreak. To address these key public health concerns, numerous countries have expressed interest in conducting or are currently conducting clinical and epidemiological studies. Here we report on a large international and multidisciplinary collaborative effort to generate standardised clinical and epidemiological research protocols and questionnaires for Zika virus.
The global EMD638683 has recognised the need for standardised investigations and data collection following the outbreaks of avian influenza (H5N1, H7N9) and during the H1N1 pandemic of 2009. Since 2011, two international and well-represented networks (the International Severe Acute Respiratory and Emerging Infection Consortium [] and the Consortium for the Standardization of Influenza Seroepidemiology []) have been working in collaboration with WHO towards the standardisation of clinical, epidemiological, and laboratory methods used in outbreaks.
The process by which these standardised research protocols were generated is described in the . Briefly, WHO, Institut Pasteur, and CONSISE used existing provided by numerous institutions to generate six full research protocol drafts that harmonise (standardise) the key methodological aspects of each study design (). A seventh protocol (clinical characterisation protocol for Zika virus infection in the context of co-circulating arboviruses) is also in development.
The standardised research protocols have been shared with a number of international experts involved in Zika virus research. In June, 2016, a face-to-face meeting in Mexico City, Mexico, attended by more than 60 researchers and public health professionals from 14 countries across the Americas and Europe (see for agenda of meeting and list of participants) discussed in detail the research methodologies being proposed in the protocols and agreed on points for harmonisation (). Following feedback from this meeting with key international scientists and policymakers, the protocols were modified and are now freely available on the WHO, PAHO, and other partners\' websites to anyone who would like to use them, under a Creative Commons license.
Zika virus, an emerging arbovirus similar to dengue virus and chikungunya virus, is mostly transmitted by and mosquitoes. Since the first
reported dengue case in 1994, Pakistan has faced multiple outbreaks of dengue and chikungunya. Despite increasing control efforts, breeding sites for vectors are now found in major cities.
Besides exhibiting similar clinical signs to those of dengue and chikungunya, Zika virus disease is associated with congenital microcephaly and Guillain-Barré syndrome (GBS), a matter of utmost concern. Of particular note is a recent increase in GBS cases of unknown aetiology in the Pakistani population. Although no clinical cases of Zika virus disease have been notified in Pakistan, the first serological traces of infection date back to 1983. An important factor that might obscure Zika virus detection is the lack of a national, unified arbovirus surveillance system. Moreover, in patients showing symptoms of arbovirus-like fever, Zika virus diagnostic tests are currently not included in clinical protocols and medical practitioners are more inclined to investigate for dengue virus. Also, 61% of the Pakistani population lives in rural areas where fevers, rashes, or joint pains are not considered as red flag signs for a hospital visit. Although the awareness level has increased following campaigns against dengue, many people remain oblivious to the health threats posed by arboviruses.
We did a qualitative analysis to estimate the potential risk of Zika virus introduction
into the country. We used the circlize statistical package for R software to visualise incoming traffic (logarithm of relative passenger volume) to Pakistani airports from countries characterised as Zika-virus-infected by the as of Sept 1, 2016. In a given country, only infected areas were considered (eg, Miami, FL, in the USA). Data on incoming passenger travel volume were obtained from the International Air Transport Association for 2015 (direct and indirect routes with stopovers).
We found that the highest proportion of high-risk travellers arrived from Singapore (). Miami, FL, USA, and Brazil were the next two largest contributors to arrivals. While fewer in numbers, travellers to Pakistan converged from an additional 23 Zika-virus-infected regions. All international Pakistani airports are possible entry routes for Zika virus, and all are located in areas where moquitoes breed (), indicating the potential for onward transmission.