- Email: [email protected]
Health and human rights in Cuba
the development of networks to undertake such trials. These are vital: children have as much right as adults do to properly assessed medicine.
*Esse N Menson, A Sarah Walker, Diana M Gibb [email protected] MRC Clinical Trials Unit, HIV Division, London NW1 2DA, UK 1
2
3
4
5
Caldwell PHY, Murphy SB, Butow ON, Craig JC. Clinical trials in children. Lancet 2004; 364: 803–11. Tin W, Walker S, Lacamp C. Oxygen monitoring in preterm babies: too high, too low? Paediatr Respir Rev 2003; 4: 9–14. Purdy IB. Perinatal corticosteroids: a review of the research, part II: postnatal administration. Neonatal Netw 2004; 23: 13–25. Paediatric European Network for Treatment of AIDS (PENTA). Comparison of dual nucleoside-analogue reverse-transcriptase inhibitor regimens with and without nelfinavir in children with HIV-1 who have not previously been treated: the PENTA 5 randomised trial. Lancet 2002; 359: 733–40. Sharland M, Blanche S, Castelli G, Ramos J, Gibb DM, for the PENTA Steering Committee. PENTA guidelines for the use of antiretroviral therapy. HIV Med 2004; 5: 61–86 .
Health and human rights in Cuba In his Health and Human Rights article (Sept 11, p 1007),1 Richard Garfield describes how the US blockade and US humanitarian policies towards Cuba only serve domestic interests. We feel his analysis needs to be completed and, on some points, corrected. First, there are factual errors. After the collapse of the Soviet Union, Cuba entered a period of economic difficulties, aggravated by the tightening of the US blockade. This period had serious consequences on all socioeconomic sectors. In the health sector, it led to a rise in mortality in those aged 65 years and older, as Garfield indicates, and also to an increase in the proportion of low birthweight infants (from 7·3% in 1989 to 9% in 1994) and in the tuberculosis incidence (from 5 per 100 000 in 1989 to 15 per 100000 in 1995). From 1995 onwards the economy grew, and health indicators started to recuperate quickly. In 2003, the proportion of low birthweight babies was 5·5% and the tuberwww.thelancet.com Vol 364 December 18/25, 2004
culosis incidence rate had decreased to 7·2 per 100000. Also, mortality among those aged older than 65 years decreased again from 54·9 per 1000 in 1996 to 47·5 per 1000 in 2003—ie, lower than the 48·4 per 1000 of 1989.2 Garfield sees, in our view, a non-existent contradiction between child care and mortality rate in those aged 65 years and older. Second, Garfield’s affirmation that Cuba’s “impressive health cannot go on forever” needs to be put in the right perspective. It may not go on forever under a tightened blockade that would entail still more economic constraints, restrictions on investments in health, and direct obstruction of the import of medical supplies. In that sense, Garfield’s emphasis on the US policy towards Cuba in function of its domestic electoral interests is important but onesided, since for more than four decades all US governments have continued to defend their interests by isolating, undermining, or invading the island. Since the 1960s, this aggressive US policy has damaged the Cuban economy by more than US$79 billion.3 Third, bringing in more humanitarian non-governmental organisations— now or in a post-Castro era—is no solution. The material and financial input from solidarity organisations since the crisis of the 1990s is only a small support of massive local efforts. Moreover, Cuba is itself reaching out with humanitarian medical aid worldwide. Today, more than 15 000 Cuban physicians are working in 64 countries, mainly in Latin America and Africa. Finally, to advance human rights, the US Government needs to do more than free up restriction on the travel of its health workers and the sale of medical goods to Cuba. Cuba has no shortage of medical personnel. Furthermore, freeing the sale of medical supplies would be an important, but only a small, first step. The USA should end its embargo against Cuba, which for more than 40 years has infringed international and humanitarian law, and has been condemned by numerous resolutions of
Sofie Blancke, Medicine for the People, Belgium
Correspondence
San Juan de los Baños, Cuba
the United Nation’s General Assembly.4 Cuba will be much more prosperous, stable, and healthy from the day the USA decides to respect its sovereignty.
*Pol De Vos, Mariano Bonet, Patrick Van der Stuyft [email protected] *Institute for Tropical Medicine, Antwerp, Belgium (PDV, PVdS); and Institute for Hygiene, Epidemiology and Microbiology, Havana, Cuba (MB) 1
2 3
4
Garfield R. Health care in Cuba and the manipulation of humanitarian imperatives. Lancet 2004; 364: 1007. Ministry of Public Health. Anuario Estadístico 2003. Havana: Ministry of Public Health, 2004. Perez-Roque F. Report to the General Assembly of the United Nations, October 2004. http:// www.cubafriends.ca/news/UNres_10_28.php (accessed Nov 11, 2004). United Nations General Assembly. Report on the vote to end the US embargo of Cuba, Oct 28, 2004. http://www.un.org/News/Press/ docs/2004/ga10288.doc.htm (accessed Nov 11, 2004).
Author’s reply Pol De Vos and colleagues further detail important health developments in Cuba. There is much to learn from Cuba’s successful targeted programmes for reducing low birthweights, infant mortality, and mortality among those aged 65 years and older after 1995. But important differences between child and elder health are more than imaginary. In times of economic crisis, when a strong state designs effective policies, health of young children is easier and cheaper to improve than health of elderly individuals. In Cuba, the interruption of mortality decline in infants was far smaller, of shorter duration, and accounted for fewer 2177
Correspondence
excess deaths than in elderly individuals. The US embargo is not the only constraint to further health improvements in Cuba. I agree that non-governmental organisations can offer no better medical expertise than Cuba already has. What they and other institutions can provide is an opening to overcome the internal blockade that isolates the country unnecessarily. Many of the doctors who work abroad might do so fundamentally for economic reasons, since salaries in Cuba offer little more than subsistence. To advance human rights, Cuba needs a more viable, flexible, and open economic system. Although Washington has often acted to limit such an option, many of the most important limitations are imposed by Havana. Those who defend the existing rigid economic structures could unintentionally assist those in the CubanAmerican community and their backers who aim to overthrow Cuba’s political system. These groups have generally shown only scorn for the effective network of public-health services that system has created.
Richard Garfield [email protected] Columbia University, Box 6, 630 West 168th Street, NY 10032, USA
conventional methods. The fact that 20% of the individuals without inflammatory bowel disease (IBD) are positive with this technique suggests a poor diagnostic specificity. Conventional PCR is capable of detecting less than 100 copies of DNA template per reaction, which is more than suitable for this type of study; nested PCR can detect a single copy, which could constitute environmental contamination and might, therefore, explain the results in the control group. The increase in PCR positivity in IBD might also be due to the raised transfer of microorganisms and fragmentary components from the bowel to the blood in patients with both Crohn’s disease and ulcerative colitis, who have a leaky epithelial intestinal barrier. Naser and colleagues1 could have controlled for this eventuality by testing for the presence of other environmental organisms in blood with the same technique and by including controls with diffuse colitis secondary to causes other than IBD. MAP might play a part in Crohn’s disease, but a much more carefully designed experiment than this one is needed to convincingly support the notion.
*Jim Huggett, Keertan Dheda, Alimuddin Zumla, Graham Rook [email protected]
2178
Crohn’s disease and MAP
Centre for Infectious Diseases and International Health, Windeyes Institute of Medical Research, London W1T 4JF, UK
Saleh Naser and colleagues (Sept 18, p 1039)1 have studied the controversial link between Mycobacterium avium subspecies paratuberculosis (MAP) and Crohn’s disease. We welcome developments in this area, but are concerned by their use of nested PCR to identify MAP, and the absence of appropriate controls. Nested PCR is used to detect DNA in samples in which the genetic material might be damaged or in which inhibitors might be present due to the extraction technique used—ie, archaeological samples.2 The technique is too often used to improve poorly optimised
1
2
Naser SA, Ghobrial G, Romero C, Valentine JF. Culture of Mycobacterium avium subspecies paratuberculosis from the blood of patients with Crohn’s disease. Lancet 2004; 364: 1039–44. Fletcher HA, Donoghue HD, Holton J, Pap I, Spigelman M. Widespread occurrence of Mycobacterium tuberculosis DNA from 18th–19th century Hungarians. Am J Phys Anthropol 2003; 120: 144–52.
Authors’ reply Jim Huggett and colleagues raise several points that deserve comment and clarification. We agree that conventional PCR should detect MAP. However, by using the more sensitive technique we avoided some of the risks of false negative results given the unknown quantity
of MAP DNA in our samples. That MAP DNA was detected in the blood from those with and without Crohn’s disease suggests to us that environmental exposure to MAP is common. We eliminated the possibility of laboratory contamination by running negative controls with all PCR assays, including controls for the DNA isolation steps, as well as running PCR reactions without template DNA. In all instances, the negative controls gave a negative result. Blood is considered sterile and can contain some yet to be defined quantity of bacterial DNA,1,2 and we agree that blood tests for MAP DNA are not likely to have the specificity needed for use as a test for those with active MAP bacteraemia. The focus of discussion should not be on the blood DNA results, however, but on the more important culture results. In our outpatient population, 50% of the patients with Crohn’s disease, 22% of those with ulcerative colitis, and none of those with non-IBD had live MAP in peripheral blood. Sequencing of the IS900 PCR product from the cultures revealed that none of the sequences matched the strain of MAP that we used in our laboratory. We stated in our discussion that our findings did not prove that MAP is a cause of Crohn’s disease. We agree that an increase in intestinal permeability might contribute to the blood DNA results observed in the patients with Crohn’s disease. However, conventional wisdom suggests that the patients with Crohn’s disease should not be bacteraemic with MAP. Furthermore, since blood is normally sterile, we aseptically collected and inoculated the blood samples into culture media, which would support the growth of other microorganisms, if present. Therefore, if the presence of viable MAP in blood is caused by a leaky epithelial wall, we would expect to see other normal flora microorganisms growing too. That was not the case even from samples from healthy controls. Hypotheses for our findings are that patients with Crohn’s disease have a defect in microbial killing, thus resultwww.thelancet.com Vol 364 December 18/25, 2004
*Esse N Menson, A Sarah Walker, Diana M Gibb [email protected] MRC Clinical Trials Unit, HIV Division, London NW1 2DA, UK 1
2
3
4
5
Caldwell PHY, Murphy SB, Butow ON, Craig JC. Clinical trials in children. Lancet 2004; 364: 803–11. Tin W, Walker S, Lacamp C. Oxygen monitoring in preterm babies: too high, too low? Paediatr Respir Rev 2003; 4: 9–14. Purdy IB. Perinatal corticosteroids: a review of the research, part II: postnatal administration. Neonatal Netw 2004; 23: 13–25. Paediatric European Network for Treatment of AIDS (PENTA). Comparison of dual nucleoside-analogue reverse-transcriptase inhibitor regimens with and without nelfinavir in children with HIV-1 who have not previously been treated: the PENTA 5 randomised trial. Lancet 2002; 359: 733–40. Sharland M, Blanche S, Castelli G, Ramos J, Gibb DM, for the PENTA Steering Committee. PENTA guidelines for the use of antiretroviral therapy. HIV Med 2004; 5: 61–86 .
Health and human rights in Cuba In his Health and Human Rights article (Sept 11, p 1007),1 Richard Garfield describes how the US blockade and US humanitarian policies towards Cuba only serve domestic interests. We feel his analysis needs to be completed and, on some points, corrected. First, there are factual errors. After the collapse of the Soviet Union, Cuba entered a period of economic difficulties, aggravated by the tightening of the US blockade. This period had serious consequences on all socioeconomic sectors. In the health sector, it led to a rise in mortality in those aged 65 years and older, as Garfield indicates, and also to an increase in the proportion of low birthweight infants (from 7·3% in 1989 to 9% in 1994) and in the tuberculosis incidence (from 5 per 100 000 in 1989 to 15 per 100000 in 1995). From 1995 onwards the economy grew, and health indicators started to recuperate quickly. In 2003, the proportion of low birthweight babies was 5·5% and the tuberwww.thelancet.com Vol 364 December 18/25, 2004
culosis incidence rate had decreased to 7·2 per 100000. Also, mortality among those aged older than 65 years decreased again from 54·9 per 1000 in 1996 to 47·5 per 1000 in 2003—ie, lower than the 48·4 per 1000 of 1989.2 Garfield sees, in our view, a non-existent contradiction between child care and mortality rate in those aged 65 years and older. Second, Garfield’s affirmation that Cuba’s “impressive health cannot go on forever” needs to be put in the right perspective. It may not go on forever under a tightened blockade that would entail still more economic constraints, restrictions on investments in health, and direct obstruction of the import of medical supplies. In that sense, Garfield’s emphasis on the US policy towards Cuba in function of its domestic electoral interests is important but onesided, since for more than four decades all US governments have continued to defend their interests by isolating, undermining, or invading the island. Since the 1960s, this aggressive US policy has damaged the Cuban economy by more than US$79 billion.3 Third, bringing in more humanitarian non-governmental organisations— now or in a post-Castro era—is no solution. The material and financial input from solidarity organisations since the crisis of the 1990s is only a small support of massive local efforts. Moreover, Cuba is itself reaching out with humanitarian medical aid worldwide. Today, more than 15 000 Cuban physicians are working in 64 countries, mainly in Latin America and Africa. Finally, to advance human rights, the US Government needs to do more than free up restriction on the travel of its health workers and the sale of medical goods to Cuba. Cuba has no shortage of medical personnel. Furthermore, freeing the sale of medical supplies would be an important, but only a small, first step. The USA should end its embargo against Cuba, which for more than 40 years has infringed international and humanitarian law, and has been condemned by numerous resolutions of
Sofie Blancke, Medicine for the People, Belgium
Correspondence
San Juan de los Baños, Cuba
the United Nation’s General Assembly.4 Cuba will be much more prosperous, stable, and healthy from the day the USA decides to respect its sovereignty.
*Pol De Vos, Mariano Bonet, Patrick Van der Stuyft [email protected] *Institute for Tropical Medicine, Antwerp, Belgium (PDV, PVdS); and Institute for Hygiene, Epidemiology and Microbiology, Havana, Cuba (MB) 1
2 3
4
Garfield R. Health care in Cuba and the manipulation of humanitarian imperatives. Lancet 2004; 364: 1007. Ministry of Public Health. Anuario Estadístico 2003. Havana: Ministry of Public Health, 2004. Perez-Roque F. Report to the General Assembly of the United Nations, October 2004. http:// www.cubafriends.ca/news/UNres_10_28.php (accessed Nov 11, 2004). United Nations General Assembly. Report on the vote to end the US embargo of Cuba, Oct 28, 2004. http://www.un.org/News/Press/ docs/2004/ga10288.doc.htm (accessed Nov 11, 2004).
Author’s reply Pol De Vos and colleagues further detail important health developments in Cuba. There is much to learn from Cuba’s successful targeted programmes for reducing low birthweights, infant mortality, and mortality among those aged 65 years and older after 1995. But important differences between child and elder health are more than imaginary. In times of economic crisis, when a strong state designs effective policies, health of young children is easier and cheaper to improve than health of elderly individuals. In Cuba, the interruption of mortality decline in infants was far smaller, of shorter duration, and accounted for fewer 2177
Correspondence
excess deaths than in elderly individuals. The US embargo is not the only constraint to further health improvements in Cuba. I agree that non-governmental organisations can offer no better medical expertise than Cuba already has. What they and other institutions can provide is an opening to overcome the internal blockade that isolates the country unnecessarily. Many of the doctors who work abroad might do so fundamentally for economic reasons, since salaries in Cuba offer little more than subsistence. To advance human rights, Cuba needs a more viable, flexible, and open economic system. Although Washington has often acted to limit such an option, many of the most important limitations are imposed by Havana. Those who defend the existing rigid economic structures could unintentionally assist those in the CubanAmerican community and their backers who aim to overthrow Cuba’s political system. These groups have generally shown only scorn for the effective network of public-health services that system has created.
Richard Garfield [email protected] Columbia University, Box 6, 630 West 168th Street, NY 10032, USA
conventional methods. The fact that 20% of the individuals without inflammatory bowel disease (IBD) are positive with this technique suggests a poor diagnostic specificity. Conventional PCR is capable of detecting less than 100 copies of DNA template per reaction, which is more than suitable for this type of study; nested PCR can detect a single copy, which could constitute environmental contamination and might, therefore, explain the results in the control group. The increase in PCR positivity in IBD might also be due to the raised transfer of microorganisms and fragmentary components from the bowel to the blood in patients with both Crohn’s disease and ulcerative colitis, who have a leaky epithelial intestinal barrier. Naser and colleagues1 could have controlled for this eventuality by testing for the presence of other environmental organisms in blood with the same technique and by including controls with diffuse colitis secondary to causes other than IBD. MAP might play a part in Crohn’s disease, but a much more carefully designed experiment than this one is needed to convincingly support the notion.
*Jim Huggett, Keertan Dheda, Alimuddin Zumla, Graham Rook [email protected]
2178
Crohn’s disease and MAP
Centre for Infectious Diseases and International Health, Windeyes Institute of Medical Research, London W1T 4JF, UK
Saleh Naser and colleagues (Sept 18, p 1039)1 have studied the controversial link between Mycobacterium avium subspecies paratuberculosis (MAP) and Crohn’s disease. We welcome developments in this area, but are concerned by their use of nested PCR to identify MAP, and the absence of appropriate controls. Nested PCR is used to detect DNA in samples in which the genetic material might be damaged or in which inhibitors might be present due to the extraction technique used—ie, archaeological samples.2 The technique is too often used to improve poorly optimised
1
2
Naser SA, Ghobrial G, Romero C, Valentine JF. Culture of Mycobacterium avium subspecies paratuberculosis from the blood of patients with Crohn’s disease. Lancet 2004; 364: 1039–44. Fletcher HA, Donoghue HD, Holton J, Pap I, Spigelman M. Widespread occurrence of Mycobacterium tuberculosis DNA from 18th–19th century Hungarians. Am J Phys Anthropol 2003; 120: 144–52.
Authors’ reply Jim Huggett and colleagues raise several points that deserve comment and clarification. We agree that conventional PCR should detect MAP. However, by using the more sensitive technique we avoided some of the risks of false negative results given the unknown quantity
of MAP DNA in our samples. That MAP DNA was detected in the blood from those with and without Crohn’s disease suggests to us that environmental exposure to MAP is common. We eliminated the possibility of laboratory contamination by running negative controls with all PCR assays, including controls for the DNA isolation steps, as well as running PCR reactions without template DNA. In all instances, the negative controls gave a negative result. Blood is considered sterile and can contain some yet to be defined quantity of bacterial DNA,1,2 and we agree that blood tests for MAP DNA are not likely to have the specificity needed for use as a test for those with active MAP bacteraemia. The focus of discussion should not be on the blood DNA results, however, but on the more important culture results. In our outpatient population, 50% of the patients with Crohn’s disease, 22% of those with ulcerative colitis, and none of those with non-IBD had live MAP in peripheral blood. Sequencing of the IS900 PCR product from the cultures revealed that none of the sequences matched the strain of MAP that we used in our laboratory. We stated in our discussion that our findings did not prove that MAP is a cause of Crohn’s disease. We agree that an increase in intestinal permeability might contribute to the blood DNA results observed in the patients with Crohn’s disease. However, conventional wisdom suggests that the patients with Crohn’s disease should not be bacteraemic with MAP. Furthermore, since blood is normally sterile, we aseptically collected and inoculated the blood samples into culture media, which would support the growth of other microorganisms, if present. Therefore, if the presence of viable MAP in blood is caused by a leaky epithelial wall, we would expect to see other normal flora microorganisms growing too. That was not the case even from samples from healthy controls. Hypotheses for our findings are that patients with Crohn’s disease have a defect in microbial killing, thus resultwww.thelancet.com Vol 364 December 18/25, 2004