- Email: [email protected]
Yellow fever vaccination coverage heterogeneities in Luanda province, Angola
Comment
in southeast Asia (11·1%, 95% CI 6·8–15·3) and highest in Africa (22·4%, 18·1–26·7). They also identified differences in serotype distribution in European and American studies compared with other regions, with lower serotypes Ia, Ib, and III (mean prevalence estimate 55·0% [95% CI 52·3–57·7] in the Americas and 58·3% [52·2–64·5] in Europe), mainly as a result of a higher proportion of serotype II isolates. At first glance, these variations seem to match what is already known about disease estimates, but is this the whole story? Using the data from their study, Kwatra and colleagues11 developed an algorithm to estimate disease incidence based on maternal colonisation data. They estimated that the disease burden in southeast Asia would be expected to be about one per 1000 livebirths. However, the actual estimate is much lower (0·02 per 1000 livebirths).12 Thus, other factors are likely to affect disease prevalence. Maternal antibodies are a key component in disease protection13 and, together with differing serotype virulence, might account for the divergence between maternal colonisation and infant disease. Variation in maternal colonising serotypes and subsequent development of antibody is a plausible explanation. Acquisition of group B streptococcus during pregnancy seems to be related to increased functional antibody activity, which might then protect infants from becoming colonised and subsequently developing group B streptococcal disease.14 However, whether this is the only factor is not fully understood. If a maternal vaccine is to move towards licensure, the global scientific community must continue to investigate the role of other factors that might be responsible for differences in disease incidence. Only by working together to investigate the role of colonisation and antibody in protection from infant group B streptococcal disease will we finally start to make inroads in reducing the risk
of death from this preventable disease. The human and economic cost of not doing so is too great to bear. Kirsty Le Doare Centre for International Child Health, Imperial College, London, UK [email protected] I am funded by a Wellcome Trust Clinical Research Training Fellowship and a Thrasher Foundation Award. 1 2
3
4
5
6
7 8 9
10 11
12
13
14
WHO. Every newborn: an action plan to end preventable deaths. Geneva: World Health Organization, 2015. UK National Screening Committee. Screening for group B streptococcal infection in pregnancy: external review against programme appraisal criteria for the UK National Screening Committee (UK NSC). 2012. http://legacy.screening.nhs.uk/policydb_download.php?doc=499 (accessed April 4, 2016). Verani JR, McGee L, Schrag SJ, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group B streptococcal disease—revised guidelines from CDC, 2010. MMWR Recomm Rep 2010; 59: 1–36. Bedford H, de Louvois J, Halket S, Peckham C, Hurley R, Harvey D. Meningitis in infancy in England and Wales: follow up at age 5 years. BMJ 2001; 323: 533–36. Dagnew AF, Cunnington MC, Dube Q, et al. Variation in reported neonatal group B streptococcal disease incidence in developing countries. Clin Infect Dis 2012; 55: 91–102. Le Doare K, Jarju S, Darboe S, et al. Risk factors for group B streptococcus colonisation and disease in Gambian women and their infants. J Infect 2016; 72: 283–94. Le Doare K, Heath PT. An overview of global GBS epidemiology. Vaccine 2013; 31 (suppl 4): D7–12. Johri AK, Paoletti LC, Glaser P, et al. Group B streptococcus: global incidence and vaccine development. Nat Rev Microbiol 2006; 4: 932–42. Seale AC, Mwaniki M, Newton CR, Berkley JA. Maternal and early onset neonatal bacterial sepsis: burden and strategies for prevention in sub-Saharan Africa. Lancet Infect Dis 2009; 9: 428–38. Stoll BJ, Schuchat A. Maternal carriage of group B streptococci in developing countries. Pediatr Infect Dis J 1998; 17: 499–503. Kwatra G, Cunnington MC, Merrall E, et al. Prevalence of maternal colonisation with group B streptococcus: a systematic review and meta-analysis. Lancet Infect Dis 2016; published online May 25. DOI:10.1016/S1473-3099(16)30055-X. Edmond KM, Kortsalioudaki C, Scott S, et al. Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta-analysis. Lancet 2012; 379: 547–56. Baker CJ, Carey VJ, Rench MA, et al. Maternal antibody at delivery protects neonates from early onset group B streptococcal disease. J Infect Dis 2014; 209: 781–88. Kwatra G, Adrian PV, Shiri T, Buchmann EJ, Cutland CL, Madhi SA. Serotype-specific acquisition and loss of group B streptococcus recto-vaginal colonization in late pregnancy. PLoS One 2014; 9: e98778.
Yellow fever vaccination coverage heterogeneities in Luanda province, Angola Although the latest yellow fever outbreak appears to be approaching a close, nearly 2000 suspected and confirmed cases have been reported in Angola since December, 2015.1 Aggressive vaccination campaigns, coordinated by the Angolan Ministry of Health (MOH) www.thelancet.com/infection Vol 16 September 2016
and WHO in the highly affected Luanda province, have been crucial to outbreak mitigation; as of April 10, 2016, 5·9 million (90%) individuals of the province-level target population (6·6 million) were reported to have been vaccinated.1 993
Comment
Proportion of susceptible population (%)
100
Vaccinated to date (%) Threshold vaccination (%)
VTh =
95
85 80 75 70 65 60 0 12
13
14
15
16
17
18
19
20
21
22
23
Serial interval used (days)
Figure: Estimated vaccination coverage in the truly susceptible population Current vaccination coverage and threshold vaccination rate for outbreak elimination was estimated using a range (12–23 days) of serial interval lengths.
However, pockets of undervaccination pose a potential challenge for disease elimination. Eight of 12 districts in Luanda province vaccinated less than half of their district-level target populations.1 In addition to these heterogeneities in geographical vaccination coverage, susceptibility among individuals throughout the target population (ie, Luanda province) is likely to be heterogeneous as well. For example, because yellow fever is a vector-borne disease, members of the target population who work outdoors might possess a higher risk of infection than those who do not; as a result, the population that is truly susceptible to yellow fever only comprises a fraction of the target population. If the truly susceptible fraction of the target population is over-represented in currently undervaccinated districts, the outbreak could continue to smoulder, despite a 90% province-level vaccination rate. When vaccination is the primary method of disease control, and the effectiveness of the vaccine (VE) is known, the percentage of the truly susceptible population that has been vaccinated (V) during the course of a given outbreak can be evaluated:2 1–(RE/R0) VE
Where R0 and RE are the basic and effective (observed) reproductive numbers associated with the outbreak of interest. The threshold vaccination rate necessary to eliminate sustained transmission (VTh) and prevent future localised outbreaks can also be determined:3 994
VE
90
0
V=
1–(1/R0)
To assess V and VTh for the ongoing yellow fever outbreak in Angola, disease incidence data were obtained from a WHO Situation Report issued on April 10, 2016. The incidence decay and exponential adjustment (IDEA) model was then used to estimate R0 and RE.4,5 A serial interval range of 12–23 days was used to parameterise the model (appendix). Solutions for R0 ranged from 4·5 to 19·8, and for RE from 1·7 to 3·6. When a vaccine effectiveness rate of 99% was used,6 V ranged from 63% to 83% and VTh ranged from 79% to 96% (figure). Although our R0 estimates fall within the bounds of previous work,7 our vaccination coverage analysis is limited by the assumption that vaccination has been the primary method of disease control during the course of the ongoing yellow fever outbreak in Angola. Given the aggressiveness of the 2016 MOH and WHO vaccination campaigns, this assumption seems reasonable; however, if it does not hold true in reality, vaccination coverage of the truly susceptible population might be even lower than our estimated range (63–83%). In either event, a substantial portion of the truly susceptible population is likely to remain at risk owing to overvaccination in some districts and undervaccination in others.1 In view of the current global yellow fever vaccine shortage, undervaccinated districts in Luanda province are unlikely to achieve 100% vaccination.8 These districts might continue to experience sustained transmission, thus increasing the likelihood of exportation events to other countries. Kraemer and colleagues published a study9 in 2015 showing that vector viability is rapidly growing across vast expanses of the Americas, Africa, and Asia. Compounded by existing vaccine shortages, an exportation event into these regions—especially those with previously unexposed human populations—could be devastating. Exportation of yellow fever virus cases from Angola has already resulted in a large secondary outbreak in the neighbouring Democratic Republic of the Congo.8 Meanwhile, Uganda is battling a separate but concurrent yellow fever outbreak and has requested additional vaccine stock.8 Vaccine shortages for many infectious diseases will presumably occur during the next several decades, and yellow fever should serve as www.thelancet.com/infection Vol 16 September 2016
Comment
a case study. Vaccine production should be prioritised to effectively address future outbreaks of yellow fever and other vaccine-preventable diseases. However, in low-supply settings, our findings suggest that smallerscale (eg, district-level) coverage heterogeneities—as opposed to larger scale (eg, province-level) vaccination rates—should be carefully considered when developing and monitoring vaccine allocation strategies. *Maimuna S Majumder, Colleen M Nguyen, Sumiko R Mekaru, John S Brownstein Boston Children’s Hospital, Boston, MA, USA (MSM, CMN, SRM, JSB); Massachusetts Institute of Technology, Cambridge, MA, USA (MSM); Epidemico, Boston, MA, USA (SRM); and Harvard Medical School, Boston, MA, USA (JSB) [email protected]
1
2
3 4
5
6 7
8
We declare no competing interests. This work was supported by the US National Library of Medicine of the National Institutes of Health (R01LM010812). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
9
WHO Africa. Situation report: yellow fever outbreak in Angola, 11 April 2016. http://www.afro.who.int/en/yellow-fever/sitreps/item/8508situation-report-yellow-fever-outbreak-in-angola-11-april-2016.html (accessed April 21, 2016). Majumder MS, Cohn EL, Mekaru SR, Huston JE, Brownstein JS. Substandard vaccination compliance and the 2015 measles outbreak. JAMA Pediatr 2015; 169: 494–95. Fine P, Eames K, Heymann DL. “Herd immunity”: a rough guide. Clin Infect Dis 2011; 52: 911–16. Fisman DN, Hauck TS, Tuite AR, Greer AL. An IDEA for short term outbreak projection: nearcasting using the basic reproduction number. PLoS One 2013; 8: e83622. Majumder MS, Kluberg S, Sanitllana M, Mekaru S, Brownstein JS. 2014 Ebola outbreak: media events track changes in observed reproductive number. PLoS Curr 2015; 28: 7. WHO. Fact sheet: yellow fever. http://www.who.int/mediacentre/ factsheets/fs100/en/. (accessed April 21, 2016). Johansson MA, Arana-Vizcarrondo N, Biggerstaff BJ, Gallagher N, Marano N, Staples JE. Assessing the risk of international spread of yellow fever virus: a mathematical analysis of an urban outbreak in Asuncion, 2008. Am J Trop Med Hyg 2012; 86: 349–58. Center for Infectious Disease Research and Policy. Yellow fever in DRC linked to Angola’s growing outbreak. http://www.cidrap.umn.edu/newsperspective/2016/04/yellow-fever-drc-linked-angolas-growing-outbreak (accessed April 21, 2016). Kraemer MUG, Sinka ME, Duda KA, et al. The global distribution of the arbovirus vectors Aedes aegypti and Ae. Albopictus. eLife 2015; 4: e08347.
An international registry for women exposed to Zika virus during pregnancy: time for answers Barreto and colleagues1 proposed in their Comment in The Lancet a strategic plan of action, at the government level, to manage the present Zika virus epidemic and to increase knowledge about the infection. However, an international collaboration is needed because of the magnitude of situation. Since first suspicion in 2015, evidence suggests that Zika virus should be considered as a teratogenic agent, similarly to the toxoplasmosis, others (syphilis, varicella zoster), rubella, cytomegalovirus, herpes simplex (TORCH) agents, until proven otherwise.2 Nevertheless, many questions still remain. With potentially thousands of pregnancies affected worldwide, researchers urgently need to find answers to enable adequate patient counselling and the implementation of efficient preventive measures. In particular, the risks of materno–fetal transmission and modifying factors remain unclear. Cauchemanez and colleagues have recently estimated the risk of microcephaly to be 1% in case of infection occurring during the first trimester on the basis of a model of eight retrospective French Polynesian cases.3 During the Brazilian epidemic, microcephaly was suspected in 2% of newborn babies in the state of Pernambuco, www.thelancet.com/infection Vol 16 September 2016
independently of maternal exposure,4 and recently Brasil and colleagues reported fetal anomalies in 29% of symptomatic pregnant women.5 In the later study, fetal cerebral calcifications were reported even in case of infection occurring late in the second trimester.5 Similarly to other TORCH agents, it is likely that gestational age at time of maternal infection affects fetal transmission, with a specific exposure window in which the rates and fetal consequences are the highest. Furthermore, other TORCH agents have shown teratogenic effects in asymptomatic patients and in cases of secondary infection (eg, cytomegalovirus).6 As such, materno–fetal transmission cannot be excluded in asymptomatic patients infected with Zika virus. The range of fetal and neonatal anomalies remains unclear.6 Although association with neurological lesions is established, additional fetal malformations have been reported.6 Additionally, latent or late-onset complications in apparently asymptomatic infected newborn babies might develop later on (eg, hearing or visual deficits).6 Finally, although initially thought to be exclusively transmitted through mosquitoes, sexual and blood 995
in southeast Asia (11·1%, 95% CI 6·8–15·3) and highest in Africa (22·4%, 18·1–26·7). They also identified differences in serotype distribution in European and American studies compared with other regions, with lower serotypes Ia, Ib, and III (mean prevalence estimate 55·0% [95% CI 52·3–57·7] in the Americas and 58·3% [52·2–64·5] in Europe), mainly as a result of a higher proportion of serotype II isolates. At first glance, these variations seem to match what is already known about disease estimates, but is this the whole story? Using the data from their study, Kwatra and colleagues11 developed an algorithm to estimate disease incidence based on maternal colonisation data. They estimated that the disease burden in southeast Asia would be expected to be about one per 1000 livebirths. However, the actual estimate is much lower (0·02 per 1000 livebirths).12 Thus, other factors are likely to affect disease prevalence. Maternal antibodies are a key component in disease protection13 and, together with differing serotype virulence, might account for the divergence between maternal colonisation and infant disease. Variation in maternal colonising serotypes and subsequent development of antibody is a plausible explanation. Acquisition of group B streptococcus during pregnancy seems to be related to increased functional antibody activity, which might then protect infants from becoming colonised and subsequently developing group B streptococcal disease.14 However, whether this is the only factor is not fully understood. If a maternal vaccine is to move towards licensure, the global scientific community must continue to investigate the role of other factors that might be responsible for differences in disease incidence. Only by working together to investigate the role of colonisation and antibody in protection from infant group B streptococcal disease will we finally start to make inroads in reducing the risk
of death from this preventable disease. The human and economic cost of not doing so is too great to bear. Kirsty Le Doare Centre for International Child Health, Imperial College, London, UK [email protected] I am funded by a Wellcome Trust Clinical Research Training Fellowship and a Thrasher Foundation Award. 1 2
3
4
5
6
7 8 9
10 11
12
13
14
WHO. Every newborn: an action plan to end preventable deaths. Geneva: World Health Organization, 2015. UK National Screening Committee. Screening for group B streptococcal infection in pregnancy: external review against programme appraisal criteria for the UK National Screening Committee (UK NSC). 2012. http://legacy.screening.nhs.uk/policydb_download.php?doc=499 (accessed April 4, 2016). Verani JR, McGee L, Schrag SJ, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group B streptococcal disease—revised guidelines from CDC, 2010. MMWR Recomm Rep 2010; 59: 1–36. Bedford H, de Louvois J, Halket S, Peckham C, Hurley R, Harvey D. Meningitis in infancy in England and Wales: follow up at age 5 years. BMJ 2001; 323: 533–36. Dagnew AF, Cunnington MC, Dube Q, et al. Variation in reported neonatal group B streptococcal disease incidence in developing countries. Clin Infect Dis 2012; 55: 91–102. Le Doare K, Jarju S, Darboe S, et al. Risk factors for group B streptococcus colonisation and disease in Gambian women and their infants. J Infect 2016; 72: 283–94. Le Doare K, Heath PT. An overview of global GBS epidemiology. Vaccine 2013; 31 (suppl 4): D7–12. Johri AK, Paoletti LC, Glaser P, et al. Group B streptococcus: global incidence and vaccine development. Nat Rev Microbiol 2006; 4: 932–42. Seale AC, Mwaniki M, Newton CR, Berkley JA. Maternal and early onset neonatal bacterial sepsis: burden and strategies for prevention in sub-Saharan Africa. Lancet Infect Dis 2009; 9: 428–38. Stoll BJ, Schuchat A. Maternal carriage of group B streptococci in developing countries. Pediatr Infect Dis J 1998; 17: 499–503. Kwatra G, Cunnington MC, Merrall E, et al. Prevalence of maternal colonisation with group B streptococcus: a systematic review and meta-analysis. Lancet Infect Dis 2016; published online May 25. DOI:10.1016/S1473-3099(16)30055-X. Edmond KM, Kortsalioudaki C, Scott S, et al. Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta-analysis. Lancet 2012; 379: 547–56. Baker CJ, Carey VJ, Rench MA, et al. Maternal antibody at delivery protects neonates from early onset group B streptococcal disease. J Infect Dis 2014; 209: 781–88. Kwatra G, Adrian PV, Shiri T, Buchmann EJ, Cutland CL, Madhi SA. Serotype-specific acquisition and loss of group B streptococcus recto-vaginal colonization in late pregnancy. PLoS One 2014; 9: e98778.
Yellow fever vaccination coverage heterogeneities in Luanda province, Angola Although the latest yellow fever outbreak appears to be approaching a close, nearly 2000 suspected and confirmed cases have been reported in Angola since December, 2015.1 Aggressive vaccination campaigns, coordinated by the Angolan Ministry of Health (MOH) www.thelancet.com/infection Vol 16 September 2016
and WHO in the highly affected Luanda province, have been crucial to outbreak mitigation; as of April 10, 2016, 5·9 million (90%) individuals of the province-level target population (6·6 million) were reported to have been vaccinated.1 993
Comment
Proportion of susceptible population (%)
100
Vaccinated to date (%) Threshold vaccination (%)
VTh =
95
85 80 75 70 65 60 0 12
13
14
15
16
17
18
19
20
21
22
23
Serial interval used (days)
Figure: Estimated vaccination coverage in the truly susceptible population Current vaccination coverage and threshold vaccination rate for outbreak elimination was estimated using a range (12–23 days) of serial interval lengths.
However, pockets of undervaccination pose a potential challenge for disease elimination. Eight of 12 districts in Luanda province vaccinated less than half of their district-level target populations.1 In addition to these heterogeneities in geographical vaccination coverage, susceptibility among individuals throughout the target population (ie, Luanda province) is likely to be heterogeneous as well. For example, because yellow fever is a vector-borne disease, members of the target population who work outdoors might possess a higher risk of infection than those who do not; as a result, the population that is truly susceptible to yellow fever only comprises a fraction of the target population. If the truly susceptible fraction of the target population is over-represented in currently undervaccinated districts, the outbreak could continue to smoulder, despite a 90% province-level vaccination rate. When vaccination is the primary method of disease control, and the effectiveness of the vaccine (VE) is known, the percentage of the truly susceptible population that has been vaccinated (V) during the course of a given outbreak can be evaluated:2 1–(RE/R0) VE
Where R0 and RE are the basic and effective (observed) reproductive numbers associated with the outbreak of interest. The threshold vaccination rate necessary to eliminate sustained transmission (VTh) and prevent future localised outbreaks can also be determined:3 994
VE
90
0
V=
1–(1/R0)
To assess V and VTh for the ongoing yellow fever outbreak in Angola, disease incidence data were obtained from a WHO Situation Report issued on April 10, 2016. The incidence decay and exponential adjustment (IDEA) model was then used to estimate R0 and RE.4,5 A serial interval range of 12–23 days was used to parameterise the model (appendix). Solutions for R0 ranged from 4·5 to 19·8, and for RE from 1·7 to 3·6. When a vaccine effectiveness rate of 99% was used,6 V ranged from 63% to 83% and VTh ranged from 79% to 96% (figure). Although our R0 estimates fall within the bounds of previous work,7 our vaccination coverage analysis is limited by the assumption that vaccination has been the primary method of disease control during the course of the ongoing yellow fever outbreak in Angola. Given the aggressiveness of the 2016 MOH and WHO vaccination campaigns, this assumption seems reasonable; however, if it does not hold true in reality, vaccination coverage of the truly susceptible population might be even lower than our estimated range (63–83%). In either event, a substantial portion of the truly susceptible population is likely to remain at risk owing to overvaccination in some districts and undervaccination in others.1 In view of the current global yellow fever vaccine shortage, undervaccinated districts in Luanda province are unlikely to achieve 100% vaccination.8 These districts might continue to experience sustained transmission, thus increasing the likelihood of exportation events to other countries. Kraemer and colleagues published a study9 in 2015 showing that vector viability is rapidly growing across vast expanses of the Americas, Africa, and Asia. Compounded by existing vaccine shortages, an exportation event into these regions—especially those with previously unexposed human populations—could be devastating. Exportation of yellow fever virus cases from Angola has already resulted in a large secondary outbreak in the neighbouring Democratic Republic of the Congo.8 Meanwhile, Uganda is battling a separate but concurrent yellow fever outbreak and has requested additional vaccine stock.8 Vaccine shortages for many infectious diseases will presumably occur during the next several decades, and yellow fever should serve as www.thelancet.com/infection Vol 16 September 2016
Comment
a case study. Vaccine production should be prioritised to effectively address future outbreaks of yellow fever and other vaccine-preventable diseases. However, in low-supply settings, our findings suggest that smallerscale (eg, district-level) coverage heterogeneities—as opposed to larger scale (eg, province-level) vaccination rates—should be carefully considered when developing and monitoring vaccine allocation strategies. *Maimuna S Majumder, Colleen M Nguyen, Sumiko R Mekaru, John S Brownstein Boston Children’s Hospital, Boston, MA, USA (MSM, CMN, SRM, JSB); Massachusetts Institute of Technology, Cambridge, MA, USA (MSM); Epidemico, Boston, MA, USA (SRM); and Harvard Medical School, Boston, MA, USA (JSB) [email protected]
1
2
3 4
5
6 7
8
We declare no competing interests. This work was supported by the US National Library of Medicine of the National Institutes of Health (R01LM010812). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
9
WHO Africa. Situation report: yellow fever outbreak in Angola, 11 April 2016. http://www.afro.who.int/en/yellow-fever/sitreps/item/8508situation-report-yellow-fever-outbreak-in-angola-11-april-2016.html (accessed April 21, 2016). Majumder MS, Cohn EL, Mekaru SR, Huston JE, Brownstein JS. Substandard vaccination compliance and the 2015 measles outbreak. JAMA Pediatr 2015; 169: 494–95. Fine P, Eames K, Heymann DL. “Herd immunity”: a rough guide. Clin Infect Dis 2011; 52: 911–16. Fisman DN, Hauck TS, Tuite AR, Greer AL. An IDEA for short term outbreak projection: nearcasting using the basic reproduction number. PLoS One 2013; 8: e83622. Majumder MS, Kluberg S, Sanitllana M, Mekaru S, Brownstein JS. 2014 Ebola outbreak: media events track changes in observed reproductive number. PLoS Curr 2015; 28: 7. WHO. Fact sheet: yellow fever. http://www.who.int/mediacentre/ factsheets/fs100/en/. (accessed April 21, 2016). Johansson MA, Arana-Vizcarrondo N, Biggerstaff BJ, Gallagher N, Marano N, Staples JE. Assessing the risk of international spread of yellow fever virus: a mathematical analysis of an urban outbreak in Asuncion, 2008. Am J Trop Med Hyg 2012; 86: 349–58. Center for Infectious Disease Research and Policy. Yellow fever in DRC linked to Angola’s growing outbreak. http://www.cidrap.umn.edu/newsperspective/2016/04/yellow-fever-drc-linked-angolas-growing-outbreak (accessed April 21, 2016). Kraemer MUG, Sinka ME, Duda KA, et al. The global distribution of the arbovirus vectors Aedes aegypti and Ae. Albopictus. eLife 2015; 4: e08347.
An international registry for women exposed to Zika virus during pregnancy: time for answers Barreto and colleagues1 proposed in their Comment in The Lancet a strategic plan of action, at the government level, to manage the present Zika virus epidemic and to increase knowledge about the infection. However, an international collaboration is needed because of the magnitude of situation. Since first suspicion in 2015, evidence suggests that Zika virus should be considered as a teratogenic agent, similarly to the toxoplasmosis, others (syphilis, varicella zoster), rubella, cytomegalovirus, herpes simplex (TORCH) agents, until proven otherwise.2 Nevertheless, many questions still remain. With potentially thousands of pregnancies affected worldwide, researchers urgently need to find answers to enable adequate patient counselling and the implementation of efficient preventive measures. In particular, the risks of materno–fetal transmission and modifying factors remain unclear. Cauchemanez and colleagues have recently estimated the risk of microcephaly to be 1% in case of infection occurring during the first trimester on the basis of a model of eight retrospective French Polynesian cases.3 During the Brazilian epidemic, microcephaly was suspected in 2% of newborn babies in the state of Pernambuco, www.thelancet.com/infection Vol 16 September 2016
independently of maternal exposure,4 and recently Brasil and colleagues reported fetal anomalies in 29% of symptomatic pregnant women.5 In the later study, fetal cerebral calcifications were reported even in case of infection occurring late in the second trimester.5 Similarly to other TORCH agents, it is likely that gestational age at time of maternal infection affects fetal transmission, with a specific exposure window in which the rates and fetal consequences are the highest. Furthermore, other TORCH agents have shown teratogenic effects in asymptomatic patients and in cases of secondary infection (eg, cytomegalovirus).6 As such, materno–fetal transmission cannot be excluded in asymptomatic patients infected with Zika virus. The range of fetal and neonatal anomalies remains unclear.6 Although association with neurological lesions is established, additional fetal malformations have been reported.6 Additionally, latent or late-onset complications in apparently asymptomatic infected newborn babies might develop later on (eg, hearing or visual deficits).6 Finally, although initially thought to be exclusively transmitted through mosquitoes, sexual and blood 995