Correspondence
3
4
5
6
7
8
Nordic Outbreak Investigation Team C. Joint analysis by the Nordic countries of a hepatitis A outbreak, October 2012 to June 2013: frozen strawberries suspected. Euro Surveill 2013; 18: 20520. Sane J, MacDonald E, Vold L, Gossner C, Severi E, for the Outbreak Investigation Team. Multistate foodborne hepatitis A outbreak among European tourists returning from Egypt—need for reinforced vaccination recommendations, November 2012 to April 2013. Euro Surveill 2015; 20: 21018. European Food Safety Authority. Tracing of food items in connection to the multinational hepatitis A virus outbreak in Europe. EFSA J 2014; 12: 3821. Love DC, Casteel MJ, Meschke JS, Sobsey MD. Methods for recovery of hepatitis A virus (HAV) and other viruses from processed foods and detection of HAV by nested RT-PCR and TaqMan RT-PCR. Int J Food Microbiol 2008; 126: 221–26. Papafragkou E, Plante M, Mattison K, et al. Rapid and sensitive detection of hepatitis A virus in representative food matrices. J Virol Methods 2008; 147: 177–87. WHO. WHO position paper on hepatitis A vaccines—June, 2012. Wkly Epidemiol Rec 2012; 87: 261–76.
The study by Melissa Collier and colleagues1 documented an outbreak of hepatitis A caused by consumption of frozen pomegranate arils. Usually raw vegetables and fruits that are consumed unpeeled are associated with outbreaks due to foodborne pathogens. Pomegranate arils are well protected from outside environmental contaminants by a thick outer covering, but a processing step might have resulted in contamination with the hardy hepatitis A virus (HAV).2 However, HAV has not been detected in recovered frozen samples of pomegranate arils because sensitivity of detection from food samples by molecular methods is very low.3 Because of globalisation and increases in the export and import of processed foods between countries, there is an impending threat of transmission of foodborne pathogens from one place to another if quality of food is not assessed properly. Development of highly sensitive and specific multiplex biochip-based assays4 that can detect several foodborne pathogens in a short span of time is needed. Another important aspect that needs attention is the waning immunity of hepatitis A vaccination in adults. Although 634
vaccination against HAV is useful in protecting children from hepatitis A infection, the average age at which infection occurs is increasing.5 Thus, the vaccination policy needs to be reviewed, along with cost–benefit analysis regarding the role of vaccination in adults. We declare no competing interests.
Sapna Pahil, Kapil Goyal, *Mini P Singh [email protected] Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India (SP); Department of Medical Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, India (KG); and Department of Virology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India (MPS) 1
2
3
4
5
Collier MG, Khudyakov YE, Selvage D, et al. Outbreak of hepatitis A in the USA associated with frozen pomegranate arils imported from Turkey: an epidemiological case study. Lancet Infect Dis 2014; 14: 976–81. Hutin YJ, Pool V, Cramer EH, et al. A multistate, foodborne outbreak of hepatitis A. National Hepatitis A Investigation Team. N Engl J Med 1999; 340: 595–602. US Food and Drug Administration. Bacteriological analytical manual (BAM) 26B: detection of hepatitis A virus in foods. http:// www.fda.gov/Food/FoodScienceResearch/ LaboratoryMethods/ucm374006.htm (accessed Sept 30, 2014). Goetz G. New rapid pathogen test is user friendly. http://www.foodsafetynews. com/2012/02/new-rapid-pathogen-test-isuser-friendly/#.VCpTXerrbIU (accessed Sept 30, 2014). John TJ, Samuel R. Herd immunity and herd effect: new insights and definitions. Eur J Epidemiol 2000; 16: 601–06.
Ethics of HIV research in children In their Personal View, Seema Shah and colleagues 1 addressed ethical issues to be considered in paediatric HIV cure research. The recent rebound of HIV RNA in the so-called Mississippi baby dispelled hopes of a cure, and cautions against use of the term cure.2 In a subsequent Correspondence,3 the same investigators accepted the limits of our knowledge and the complexity of the scientific questions that remain unanswered, including the optimum time to interrupt antiretroviral
therapy (ART) to assess whether therapy initiated in acute infection can eradicate or prevent long-term HIV reservoirs. Shah and colleagues first proposed that therapy be maintained “until ample time has been given for the strategy to work on the basis of existing data”,1 and then conceded that “how long treatment should be given for the strategy to work is unclear”.3 We wish to emphasise that, although some data exist on the possible safe interruption of ART,4 current data does not inform the optimum time to interrupt infant treatment, which depends on the postulated mechanisms responsible for clearing infection—ie, postexposure prophylaxis or decay of acutely infected cells. These intricate questions can probably only be answered in prospective, experimental studies and not in observational research as suggested. Such studies entail intensive, invasive, and specialised monitoring of infants who test positive for HIV infection and necessitate lengthy and complex informed consent documents (ICD), and education of most eligible families will probably be needed. We propose that research be done only in infants at high risk of mother-to-childtransmission (MTCT); that the initial ICD should only consent for maternal or infant treatment during labour and until HIV diagnostic test results are known; and that subsequent ICDs cover research in infants with positive HIV diagnostic tests to elucidate the mechanisms of treatment effecting or failing to effect a cure, and issues pertaining to the interruption of ART. In view of the uncertainties surrounding the interruption of ART, adequate time and repetition should be allowed to ensure satisfactory comprehension. Finally, we caution that the hope and hyperbole invoked by the term cure does not distract from efforts to improve prevention of MTCT and antenatal services across the world. Since only 63% of the 1·5 million www.thelancet.com/infection Vol 15 June 2015
Correspondence
pregnant women infected with HIV in low-income and middle-income countries received effective ART in 2012,5 we support global efforts to expand and improve prevention-ofMTCT services, coupled with research and interventions directed at the social contexts that allow MTCT to continue in these communities. We declare no competing interests. This research was supported by the US National Institutes of Health (NIH; grant #1 R01 A 108366-01) and the Brocher Foundation. JC and TMR are both part of the research team of the HIV Cure group that received the NIH grant and funds a proportion of their time.
*Theresa M Rossouw, Johanna Crane, Lisa M Frenkel [email protected] Departments of Family Medicine and Immunology, University of Pretoria, Pretoria 0001, South Africa (TMR); Interdisciplinary Arts and Sciences, University of Washington Bothell, Bothell, WA, USA (JC); and Departments of Pediatrics, Laboratory Medicine and Global Health, Divisions of Infectious Diseases and Virology, University of Washington, Seattle, WA, USA (LMF) 1
2
3
4
5
Shah SK, Persaud D, Wendler DS, et al. Research into a functional cure for HIV in neonates: the need for ethical foresight. Lancet Infect Dis 2014; 14: 893–98. National Institute of Allergy and Infectious Diseases, NIH News. ‘Mississippi baby’ now has detectable HIV, researchers find. July 10, 2014. http://www.niaid.nih.gov/news/newsreleases/ 2014/pages/mississippibabyhiv.aspx. (accessed July 21, 2014). Shah SK, Persaud D, Wendler DS, et al. Research on very early ART in neonates at risk of HIV infection. Lancet Infect Dis 2014; 14: 797. Violari A, Cotton MF, Gibb DM, et al. Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med 2008; 359: 2233–44. WHO. Global update on HIV treatment 2013: results, impact and opportunities. June, 2013. http://www.who.int/hiv/data/global_ treatment_report_presentation_2013.pdf. (accessed July 21, 2014).
HIV/AIDS registration in Pakistan Meaningful national-level HIV/AIDS registration can only be imagined in Pakistan—an Islamic country of more than 185 million inhabitants, where people hesitate to discuss their sexual practices. Moreover, knowledge, attitude, and practices regarding HIV/AIDS are poor, not only within www.thelancet.com/infection Vol 15 June 2015
the general population, but also among general medical practitioners in Pakistan.1 As a result, a country previously regarded as low-prevalence but high risk has become a country with a concentrated HIV epidemic2 that is a potential threat to national and international health security. An urgent need exists to establish a national-level HIV/AIDS registry that will not only provide incidence, prevalence, and mortality data, but also solid grounds for health-care policy makers to devise appropriate screening, diagnostic, therapeutic, and prognostic strategies. After the first reported case of HIV/ AIDS in the country in 1986, the Pakistani Government formulated the National AIDS Control Program (NACP) in 1988. Since its inception, the NACP has been working for prevention and control of AIDS within the country. However, despite commendable efforts by the NACP, HIV/AIDS registration, prevention, and treatment remains a vital health concern in Pakistan, 3 probably because of limited resources. There are several areas of improvement that NACP and other stakeholders should consider. For example, the visibility and accessibility of the NACP to the general population are lacking. Moreover, and alarmingly, the website maintained by the NACP office (a major source of information for the general public and international agencies) is not informative enough to teach the general population about HIV/AIDS registration or treatment. Although the NACP claims to have provincial centres, information is inaccessible through the website. Furthermore, regular and nationwide active public information campaigns should be arranged by the NACP to address the issue effectively. Finally, and as mentioned on the NACP website, the NACP operates only 15 treatment centres in Pakistan—one federal, seven in Punjab, four in Sindh, one in Baluchistan, and two in
Khyberpakhtoonkhwa. This number of treatment centres is not enough to cover a population of more than 185 million. As a result, a large number of patients with HIV/AIDS remain unregistered in Pakistan. Moreover, no concrete data are available with respect to the number of people living with HIV, number of new HIV/AIDS registrations, and mortality status of HIV-infected patients in Pakistan. According to the NACP, the estimated number of people living with HIV in Pakistan is 97 400, whereas a 2014 Joint UN Program on HIV/AIDS report claims that 83 468 people were living with HIV at the end of 2013.2 However, these conflicting statistics are only estimates and are possibly far away from the true number. Appropriate and urgent actions must be undertaken by all stakeholders—both Pakistani and international authorities—to establish an HIV/AIDS registry in Pakistan and increase public awareness. Regular public awareness campaigns, through seminars and print and electronic media could be an important initial step in this respect. Appropriate funding is needed to revolutionise the existing operations of the NACP to render it more functional and meaningful. Moreover, because Pakistan is an Islamic state in which a large proportion of people practice religion, engagement of Islamic scholars (priests, or Maulvi) could substantially increase public awareness via sermons in mosques.
For more on the NACP see http://www.nacp.gov.pk/
We declare no competing interests.
*Muhammad Asif Qureshi, Saeed Khan, Maria Zahid, Zain Ali [email protected] Department of Pathology, Dow International Medical College, Ojha Campus, Dow University of Health Sciences, Karachi, Pakistan 1
Hussain MF, Khanani MR, Siddiqui SE, Manzar N, Raza S, Qamar S. Knowledge, attitude & practices (KAP) of general practitioners (GPs) regarding sexually transmitted diseases (STDs) and HIV/AIDS in Karachi, Pakistan. J Pak Med Assoc 2011; 61: 202–05.
635
3
4
5
6
7
8
Nordic Outbreak Investigation Team C. Joint analysis by the Nordic countries of a hepatitis A outbreak, October 2012 to June 2013: frozen strawberries suspected. Euro Surveill 2013; 18: 20520. Sane J, MacDonald E, Vold L, Gossner C, Severi E, for the Outbreak Investigation Team. Multistate foodborne hepatitis A outbreak among European tourists returning from Egypt—need for reinforced vaccination recommendations, November 2012 to April 2013. Euro Surveill 2015; 20: 21018. European Food Safety Authority. Tracing of food items in connection to the multinational hepatitis A virus outbreak in Europe. EFSA J 2014; 12: 3821. Love DC, Casteel MJ, Meschke JS, Sobsey MD. Methods for recovery of hepatitis A virus (HAV) and other viruses from processed foods and detection of HAV by nested RT-PCR and TaqMan RT-PCR. Int J Food Microbiol 2008; 126: 221–26. Papafragkou E, Plante M, Mattison K, et al. Rapid and sensitive detection of hepatitis A virus in representative food matrices. J Virol Methods 2008; 147: 177–87. WHO. WHO position paper on hepatitis A vaccines—June, 2012. Wkly Epidemiol Rec 2012; 87: 261–76.
The study by Melissa Collier and colleagues1 documented an outbreak of hepatitis A caused by consumption of frozen pomegranate arils. Usually raw vegetables and fruits that are consumed unpeeled are associated with outbreaks due to foodborne pathogens. Pomegranate arils are well protected from outside environmental contaminants by a thick outer covering, but a processing step might have resulted in contamination with the hardy hepatitis A virus (HAV).2 However, HAV has not been detected in recovered frozen samples of pomegranate arils because sensitivity of detection from food samples by molecular methods is very low.3 Because of globalisation and increases in the export and import of processed foods between countries, there is an impending threat of transmission of foodborne pathogens from one place to another if quality of food is not assessed properly. Development of highly sensitive and specific multiplex biochip-based assays4 that can detect several foodborne pathogens in a short span of time is needed. Another important aspect that needs attention is the waning immunity of hepatitis A vaccination in adults. Although 634
vaccination against HAV is useful in protecting children from hepatitis A infection, the average age at which infection occurs is increasing.5 Thus, the vaccination policy needs to be reviewed, along with cost–benefit analysis regarding the role of vaccination in adults. We declare no competing interests.
Sapna Pahil, Kapil Goyal, *Mini P Singh [email protected] Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India (SP); Department of Medical Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, India (KG); and Department of Virology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India (MPS) 1
2
3
4
5
Collier MG, Khudyakov YE, Selvage D, et al. Outbreak of hepatitis A in the USA associated with frozen pomegranate arils imported from Turkey: an epidemiological case study. Lancet Infect Dis 2014; 14: 976–81. Hutin YJ, Pool V, Cramer EH, et al. A multistate, foodborne outbreak of hepatitis A. National Hepatitis A Investigation Team. N Engl J Med 1999; 340: 595–602. US Food and Drug Administration. Bacteriological analytical manual (BAM) 26B: detection of hepatitis A virus in foods. http:// www.fda.gov/Food/FoodScienceResearch/ LaboratoryMethods/ucm374006.htm (accessed Sept 30, 2014). Goetz G. New rapid pathogen test is user friendly. http://www.foodsafetynews. com/2012/02/new-rapid-pathogen-test-isuser-friendly/#.VCpTXerrbIU (accessed Sept 30, 2014). John TJ, Samuel R. Herd immunity and herd effect: new insights and definitions. Eur J Epidemiol 2000; 16: 601–06.
Ethics of HIV research in children In their Personal View, Seema Shah and colleagues 1 addressed ethical issues to be considered in paediatric HIV cure research. The recent rebound of HIV RNA in the so-called Mississippi baby dispelled hopes of a cure, and cautions against use of the term cure.2 In a subsequent Correspondence,3 the same investigators accepted the limits of our knowledge and the complexity of the scientific questions that remain unanswered, including the optimum time to interrupt antiretroviral
therapy (ART) to assess whether therapy initiated in acute infection can eradicate or prevent long-term HIV reservoirs. Shah and colleagues first proposed that therapy be maintained “until ample time has been given for the strategy to work on the basis of existing data”,1 and then conceded that “how long treatment should be given for the strategy to work is unclear”.3 We wish to emphasise that, although some data exist on the possible safe interruption of ART,4 current data does not inform the optimum time to interrupt infant treatment, which depends on the postulated mechanisms responsible for clearing infection—ie, postexposure prophylaxis or decay of acutely infected cells. These intricate questions can probably only be answered in prospective, experimental studies and not in observational research as suggested. Such studies entail intensive, invasive, and specialised monitoring of infants who test positive for HIV infection and necessitate lengthy and complex informed consent documents (ICD), and education of most eligible families will probably be needed. We propose that research be done only in infants at high risk of mother-to-childtransmission (MTCT); that the initial ICD should only consent for maternal or infant treatment during labour and until HIV diagnostic test results are known; and that subsequent ICDs cover research in infants with positive HIV diagnostic tests to elucidate the mechanisms of treatment effecting or failing to effect a cure, and issues pertaining to the interruption of ART. In view of the uncertainties surrounding the interruption of ART, adequate time and repetition should be allowed to ensure satisfactory comprehension. Finally, we caution that the hope and hyperbole invoked by the term cure does not distract from efforts to improve prevention of MTCT and antenatal services across the world. Since only 63% of the 1·5 million www.thelancet.com/infection Vol 15 June 2015
Correspondence
pregnant women infected with HIV in low-income and middle-income countries received effective ART in 2012,5 we support global efforts to expand and improve prevention-ofMTCT services, coupled with research and interventions directed at the social contexts that allow MTCT to continue in these communities. We declare no competing interests. This research was supported by the US National Institutes of Health (NIH; grant #1 R01 A 108366-01) and the Brocher Foundation. JC and TMR are both part of the research team of the HIV Cure group that received the NIH grant and funds a proportion of their time.
*Theresa M Rossouw, Johanna Crane, Lisa M Frenkel [email protected] Departments of Family Medicine and Immunology, University of Pretoria, Pretoria 0001, South Africa (TMR); Interdisciplinary Arts and Sciences, University of Washington Bothell, Bothell, WA, USA (JC); and Departments of Pediatrics, Laboratory Medicine and Global Health, Divisions of Infectious Diseases and Virology, University of Washington, Seattle, WA, USA (LMF) 1
2
3
4
5
Shah SK, Persaud D, Wendler DS, et al. Research into a functional cure for HIV in neonates: the need for ethical foresight. Lancet Infect Dis 2014; 14: 893–98. National Institute of Allergy and Infectious Diseases, NIH News. ‘Mississippi baby’ now has detectable HIV, researchers find. July 10, 2014. http://www.niaid.nih.gov/news/newsreleases/ 2014/pages/mississippibabyhiv.aspx. (accessed July 21, 2014). Shah SK, Persaud D, Wendler DS, et al. Research on very early ART in neonates at risk of HIV infection. Lancet Infect Dis 2014; 14: 797. Violari A, Cotton MF, Gibb DM, et al. Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med 2008; 359: 2233–44. WHO. Global update on HIV treatment 2013: results, impact and opportunities. June, 2013. http://www.who.int/hiv/data/global_ treatment_report_presentation_2013.pdf. (accessed July 21, 2014).
HIV/AIDS registration in Pakistan Meaningful national-level HIV/AIDS registration can only be imagined in Pakistan—an Islamic country of more than 185 million inhabitants, where people hesitate to discuss their sexual practices. Moreover, knowledge, attitude, and practices regarding HIV/AIDS are poor, not only within www.thelancet.com/infection Vol 15 June 2015
the general population, but also among general medical practitioners in Pakistan.1 As a result, a country previously regarded as low-prevalence but high risk has become a country with a concentrated HIV epidemic2 that is a potential threat to national and international health security. An urgent need exists to establish a national-level HIV/AIDS registry that will not only provide incidence, prevalence, and mortality data, but also solid grounds for health-care policy makers to devise appropriate screening, diagnostic, therapeutic, and prognostic strategies. After the first reported case of HIV/ AIDS in the country in 1986, the Pakistani Government formulated the National AIDS Control Program (NACP) in 1988. Since its inception, the NACP has been working for prevention and control of AIDS within the country. However, despite commendable efforts by the NACP, HIV/AIDS registration, prevention, and treatment remains a vital health concern in Pakistan, 3 probably because of limited resources. There are several areas of improvement that NACP and other stakeholders should consider. For example, the visibility and accessibility of the NACP to the general population are lacking. Moreover, and alarmingly, the website maintained by the NACP office (a major source of information for the general public and international agencies) is not informative enough to teach the general population about HIV/AIDS registration or treatment. Although the NACP claims to have provincial centres, information is inaccessible through the website. Furthermore, regular and nationwide active public information campaigns should be arranged by the NACP to address the issue effectively. Finally, and as mentioned on the NACP website, the NACP operates only 15 treatment centres in Pakistan—one federal, seven in Punjab, four in Sindh, one in Baluchistan, and two in
Khyberpakhtoonkhwa. This number of treatment centres is not enough to cover a population of more than 185 million. As a result, a large number of patients with HIV/AIDS remain unregistered in Pakistan. Moreover, no concrete data are available with respect to the number of people living with HIV, number of new HIV/AIDS registrations, and mortality status of HIV-infected patients in Pakistan. According to the NACP, the estimated number of people living with HIV in Pakistan is 97 400, whereas a 2014 Joint UN Program on HIV/AIDS report claims that 83 468 people were living with HIV at the end of 2013.2 However, these conflicting statistics are only estimates and are possibly far away from the true number. Appropriate and urgent actions must be undertaken by all stakeholders—both Pakistani and international authorities—to establish an HIV/AIDS registry in Pakistan and increase public awareness. Regular public awareness campaigns, through seminars and print and electronic media could be an important initial step in this respect. Appropriate funding is needed to revolutionise the existing operations of the NACP to render it more functional and meaningful. Moreover, because Pakistan is an Islamic state in which a large proportion of people practice religion, engagement of Islamic scholars (priests, or Maulvi) could substantially increase public awareness via sermons in mosques.
For more on the NACP see http://www.nacp.gov.pk/
We declare no competing interests.
*Muhammad Asif Qureshi, Saeed Khan, Maria Zahid, Zain Ali [email protected] Department of Pathology, Dow International Medical College, Ojha Campus, Dow University of Health Sciences, Karachi, Pakistan 1
Hussain MF, Khanani MR, Siddiqui SE, Manzar N, Raza S, Qamar S. Knowledge, attitude & practices (KAP) of general practitioners (GPs) regarding sexually transmitted diseases (STDs) and HIV/AIDS in Karachi, Pakistan. J Pak Med Assoc 2011; 61: 202–05.
635
