The Coming Plague (133 page)
Authors: Laurie Garrett
162
A. W. Taylor-Robinson, R. S. Phillips, A. Severn, et al., “The Role of T
H
1 and T
H
2 Cells in a Rodent Malaria Infection,”
Science
260 (1993): 1931â34.
H
1 and T
H
2 Cells in a Rodent Malaria Infection,”
Science
260 (1993): 1931â34.
163
Y. Charoenvit, W. E. Collins, T. R. Jones, et al., “Inability of Malaria Vaccine to Induce Antibodies to a Protective Epitope Within Its Sequence,”
Science
251 (1991): 668â72; J. E. Egan, J. L. Weber, W. R. Ballou, et al., “Efficacy of Murine Malaria Sporozoite Vaccines: Implications for Human Vaccine Development,”
Science
236 (1987): 453â56; and R. Rosenberg, R. A. Wirtz, D. E. Lanar, et al., “Circumsporozoite Protein Heterogeneity in the Human Malaria Parasite
Plasmodium vivax,” Science
245 (1989): 973â76.
Science
251 (1991): 668â72; J. E. Egan, J. L. Weber, W. R. Ballou, et al., “Efficacy of Murine Malaria Sporozoite Vaccines: Implications for Human Vaccine Development,”
Science
236 (1987): 453â56; and R. Rosenberg, R. A. Wirtz, D. E. Lanar, et al., “Circumsporozoite Protein Heterogeneity in the Human Malaria Parasite
Plasmodium vivax,” Science
245 (1989): 973â76.
164
J. Lines and J. R. M. Armstrong, “For a Few Parasites More: Inoculum Size, Vector Control and Strain-Specific Immunity to Malaria,”
Parasitology Today
8 (1992): 381â83.
Parasitology Today
8 (1992): 381â83.
165
S. Kumar, L. H. Miller, and I. A. Quakyi, “Cytotoxic T Cells Specific for the Circumsporozoite Protein of
Plasmodium falciparum,” Nature
334 (1988): 258â60; and Institute of Medicine,
Malaria: Obstacles and Opportunities
(Washington, D.C.: National Academy Press, 1991).
Plasmodium falciparum,” Nature
334 (1988): 258â60; and Institute of Medicine,
Malaria: Obstacles and Opportunities
(Washington, D.C.: National Academy Press, 1991).
166
S. L. Hoffman, V. Nussenzweig, J. C. Sadoff, and R. S. Nussenzweig, “Progress Toward Malaria Preerythrocytic Vaccines,”
Science
252 (1991): 520â21.
Science
252 (1991): 520â21.
167
One theory had it that chloroquine resistance could only get so bad in a society before the humans would develop sufficient baseline immunity to keep the parasites in check. A state of tolerance developed, and the partially immune humans were able to prevent the parasites from developing
complete
resistance. See J. C. Koella, “Epidemiological Evidence for an Association Between Chloroquine Resistance of
Plasmodium falciparum
and Its Immunological Properties,”
Parasitology Today
9 (1993): 105â8.
complete
resistance. See J. C. Koella, “Epidemiological Evidence for an Association Between Chloroquine Resistance of
Plasmodium falciparum
and Its Immunological Properties,”
Parasitology Today
9 (1993): 105â8.
168
D. Hurvitz and K. Hirschhorn, “Suppression of
in vitro
Lymphocyte Responses by Chloroquine,”
New England Journal of Medicine
273 (1965): 23â26; G. Salmeron and P. E. Lipsky, “Immunosuppression Potential of Antimalarials,”
American Journal of Medicine
75 (1983): 19â24; and D. N. Taylor, C. Wasi, and K. Bernard, “Chloroquine Prophylaxis Associated with a Poor Antibody Response to Human Diploid Cell Rabies Vaccine,”
Lancet
I (1984): 1405.
in vitro
Lymphocyte Responses by Chloroquine,”
New England Journal of Medicine
273 (1965): 23â26; G. Salmeron and P. E. Lipsky, “Immunosuppression Potential of Antimalarials,”
American Journal of Medicine
75 (1983): 19â24; and D. N. Taylor, C. Wasi, and K. Bernard, “Chloroquine Prophylaxis Associated with a Poor Antibody Response to Human Diploid Cell Rabies Vaccine,”
Lancet
I (1984): 1405.
169
M. Pappaionou, D. B. Fishbein, D. W. Dreesen, et al., “Antibody Response to Preexposure Human Diploid-Cell Rabies Vaccine Given Concurrently with Chloroquine,”
New England Journal of Medicine
314 (1986): 280â84.
New England Journal of Medicine
314 (1986): 280â84.
The immune system dampening effect was not true for all types of immunizations. Nigerian children responded similarly to pneumococcal vaccines regardless of whether or not they took chloroquine. See C. Van Der Straeten and J. H. Klippel, “Antimalarials and Pneumococcal Immunization,”
New England Journal of Medicine
315 (1986): 712.
New England Journal of Medicine
315 (1986): 712.
170
An extensive study of the use of chloroquine prophylaxis on Nigerian children in 1984 yielded a puzzling result: the prophylaxed children suffered fewer cases of malaria, but were just as likely as kids who never took chloroquine to die of malaria. In this study malaria was defined as fever plus laboratory-confirmed parasite infection of the child's blood. Given that definition of malaria, there may be less contradiction than first meets the eye between a lower incidence of “malaria” in the chloroquineusing group and an equal or higher death rate. See A. Bradley-Moore, D. E. Bidwell, A. Voller, et al., “Malaria Chemoprophylaxis with Chloroquine in Young Nigerian Children,”
Annals of Tropical Medicine and Parasitology
79 (1985): 549â62.
Annals of Tropical Medicine and Parasitology
79 (1985): 549â62.
171
For further evidence of the antifever effect of chloroquine, see A. D. Brandling-Bennett, A. J. Oloo, W. M. Watkins, et al., “Chloroquine Treatment of
falciparum
Malaria in an Area of Kenya of Intermediate Chloroquine Resistance,”
Transactions of the Royal Society of Tropical Medicine and Hygiene
82 (1988): 833â37.
falciparum
Malaria in an Area of Kenya of Intermediate Chloroquine Resistance,”
Transactions of the Royal Society of Tropical Medicine and Hygiene
82 (1988): 833â37.
172
Plasmodium falciparum
could produce some of this effect. German researchers were convinced that the parasites stimulated an autoimmune response in which red blood cells were destroyed by the victim's own immune system. Their study did not, however, control for chloroquine use, so they couldn't rule out the possibility that the drug induced the observed autoimmunity. See K. Ritter, A. Kuhlencord, R. Thomssen, and W. Bommer, “Prolonged Haemolytic Anaemia in Malaria and Autoantibodies Against Triosephosphate Isomerase,”
Lancet
342 (1993): 1333â34.
could produce some of this effect. German researchers were convinced that the parasites stimulated an autoimmune response in which red blood cells were destroyed by the victim's own immune system. Their study did not, however, control for chloroquine use, so they couldn't rule out the possibility that the drug induced the observed autoimmunity. See K. Ritter, A. Kuhlencord, R. Thomssen, and W. Bommer, “Prolonged Haemolytic Anaemia in Malaria and Autoantibodies Against Triosephosphate Isomerase,”
Lancet
342 (1993): 1333â34.
There was also a hypothesis that malaria induced the immune system to release large amounts of tumor necrosis factor (TNF), a powerful human chemical that had a broad range of effects on the body. Usually researchers claimed that TNF played a role in cerebral malaria, but some also speculated it was involved in anemia. The evidence was contradictory and controversial. See R. E. Phillips and T. Solomon, “Cerebral Malaria in Children,”
Lancet
336 (1990): 1355â60; I. A. Clarke, G. Chaudri, and W. B. Cowden, “Roles of Tumour Necrosis Factor in the Illness and Pathology of Malaria,”
Transactions of the Royal Society of Tropical Medicine and Hygiene
83 (1989): 436â40; and D. Kwiatkowski, A. V. S. Hill, I. Sambou, et al., “TNF Concentration in Fatal Cerebral, Non-Fatal Cerebral, and Uncomplicated
Plasmodium falciparum
Malaria,”
Lancet
336 (1990): 1201â4.
Lancet
336 (1990): 1355â60; I. A. Clarke, G. Chaudri, and W. B. Cowden, “Roles of Tumour Necrosis Factor in the Illness and Pathology of Malaria,”
Transactions of the Royal Society of Tropical Medicine and Hygiene
83 (1989): 436â40; and D. Kwiatkowski, A. V. S. Hill, I. Sambou, et al., “TNF Concentration in Fatal Cerebral, Non-Fatal Cerebral, and Uncomplicated
Plasmodium falciparum
Malaria,”
Lancet
336 (1990): 1201â4.
173
P. B. Bloland, E. M. Lackritz, P. N. Kazembe, et al., “Beyond Chloroquine: Implications of Drug Resistance for Evaluating Malaria Therapy Efficacy and Treatment Policy in Africa,”
Journal of Infectious Diseases
167 (1993): 932â37.
Journal of Infectious Diseases
167 (1993): 932â37.
174
Even as early as 1984 there was widespread resistance in East Africa to Fansidar, particularly its component pyrimethamine. But amodiaquine and mefloquine remained useful alternatives in most of Africa well into the late 1980s. See H. C. Spencer, “Drug-Resistant Malaria: Changing Patterns Mean Difficult Decisions,”
Transactions of the Royal Society of Tropical Medicine and Hygiene
79 (1985): 748â58.
Transactions of the Royal Society of Tropical Medicine and Hygiene
79 (1985): 748â58.
175
T. Harinasuta, S. Migasen, and D. Boonag,
UNESCO First Regional Symposium on Scientific Knowledge of Tropical Parasites
. (Singapore: UNESCO, 1962).
UNESCO First Regional Symposium on Scientific Knowledge of Tropical Parasites
. (Singapore: UNESCO, 1962).
176
A. A. Sandosham, “Chloroquine-Resistant
falciparum
Malaria in Malaya,”
Singapore Medical Journal
4 (1963): 3â5.
falciparum
Malaria in Malaya,”
Singapore Medical Journal
4 (1963): 3â5.
177
P. G. Contacos, J. S. Lunn, and G. R. Coatney, “Drug-Resistant
falciparum
Malaria from Cambodia and Malaya,”
Transactions of the Royal Society of Tropical Medicine and Hygiene
57 (1963): 417â24.
falciparum
Malaria from Cambodia and Malaya,”
Transactions of the Royal Society of Tropical Medicine and Hygiene
57 (1963): 417â24.
178
UNDP/World Bank/WHO, Report of a Meeting Held in Kuala Lumpur, Malaysia, August 10â15, 1981 (Geneva: World Health Organization, 1981).
179
Ibid.
180
Centers for Disease Control, “
Plasmodium falciparum
Malaria Contracted in Thailand Resistant to Chloroquine and Sulfonamide-PyrimethamineâIllinois,”
Morbidity and Mortality Weekly Report
29 (1980): 493â94.
Plasmodium falciparum
Malaria Contracted in Thailand Resistant to Chloroquine and Sulfonamide-PyrimethamineâIllinois,”
Morbidity and Mortality Weekly Report
29 (1980): 493â94.
181
G. Watt, G. W. Long, L. P. Padre, et al., “Chloroquine and Quinine: A Randomized, Double-Blind Comparison of Efficacy and Side Effects in the Treatment of
Plasmodium falciparum
Malaria in the Philippines,”
Transactions of the Royal Society of Tropical Medicine and Hygiene
82 (1988): 205â8; and V. P. Sharma, C. Prasittisuk, and A. V. Kondrashin, “Magnitude of Forest Malaria,” in V. P. Sharma and A. V. Kondrashin, eds.,
Proceedings of an Informal Consultation Meeting WHO/ MRC 18â22 February 1991
(New Delhi: World Health Organization, 1991).
Plasmodium falciparum
Malaria in the Philippines,”
Transactions of the Royal Society of Tropical Medicine and Hygiene
82 (1988): 205â8; and V. P. Sharma, C. Prasittisuk, and A. V. Kondrashin, “Magnitude of Forest Malaria,” in V. P. Sharma and A. V. Kondrashin, eds.,
Proceedings of an Informal Consultation Meeting WHO/ MRC 18â22 February 1991
(New Delhi: World Health Organization, 1991).
182
Sharma, Prasittisuk, and Kondrashin (1991), op. cit.
183
M. K. Banerjee, N. Palikhe, B. L. Shestha, et al., in Sharma and Kondrashin, eds. (1991), op. cit.
In Burma the 1976 malarial death rate was 2.5 per 100,000. By 1989 that had risen to 12.3 per 100,000. And as had been seen in Africa, adult cerebral malaria cases increased in both number and severity. By 1989, one out of every three cerebral cases was fatal, despite drug treatment.
184
T. Chongsuphajaisiddhi, A. Sabchareon, P. Chantavanich, et al., “A Phase III Clinical Trial of Mefloquine in Children with Chloroquine-Resistant
falciparum
Malaria in Thailand,”
Bulletin of the World Health Organization
65 (1987): 223â26; H. O. Lobel, M. Miani, T. Eng, et al., “Long-Term Malaria Prophylaxis with Weekly Mefloquine,”
Lancet
341 (1993): 848â51; and R. Steffen, E. Fuchs, J. Schildknecht, et al., “Mefloquine Compared with Other Malaria Chemoprophylactic Regimens in Tourists Visiting East Africa,”
Lancet
341 (1993): 1299â1303.
falciparum
Malaria in Thailand,”
Bulletin of the World Health Organization
65 (1987): 223â26; H. O. Lobel, M. Miani, T. Eng, et al., “Long-Term Malaria Prophylaxis with Weekly Mefloquine,”
Lancet
341 (1993): 848â51; and R. Steffen, E. Fuchs, J. Schildknecht, et al., “Mefloquine Compared with Other Malaria Chemoprophylactic Regimens in Tourists Visiting East Africa,”
Lancet
341 (1993): 1299â1303.
185
S. Looareesuwan, C. Viravan, S. Vanijanonta, et al., “Randomised Trial of Artesunate and Mefloquine Alone and in Sequence for Acute Uncomplicated
falciparum
Malaria,”
Lancet
339 (1992): 821â824; and F. O. Ter Kuile, G. Dolan, F. Noster, et al., “Halofantrine Versus Mefloquine in Treatment of Multidrug-Resistant
falciparum
Malaria,”
Lancet
341 (1993): 1044â49.
falciparum
Malaria,”
Lancet
339 (1992): 821â824; and F. O. Ter Kuile, G. Dolan, F. Noster, et al., “Halofantrine Versus Mefloquine in Treatment of Multidrug-Resistant
falciparum
Malaria,”
Lancet
341 (1993): 1044â49.
186
C. M. Wilson, A. E. Serrano, A. Wasley, et al., “Amplification of a Gene Related to Mammalian
mdr
Genes in Drug-Resistant
Plasmodium falciparum
,”
Science
244 (1989): 1184â86; S. K. Martin, A. M. J. Oduola, and W. K. Mihous, “Reversal of Chloroquine Resistance in
Plasmodium falciparum
by Verapamil,”
Science
235 (1987): 899â901; C. C. Newbold, “The Path of Drug Resistance,”
Nature
345 (1990): 202â3; T. E. Wellems, L. J. Panton, I. Y. Gluzman, et al., “Chloroquine Resistance Not Linked to
mdr
-Like Genes in a
Plasmodium falciparum
Cross,”
Nature
345 (1990): 253â55; and S. J. Foote, D. E. Kyle, R. K. Martin, et al., “Several Alleles of the Multidrug-Resistance Gene Are Closely Linked to Chloroquine,”
Nature
345 (1990): 255â58.
mdr
Genes in Drug-Resistant
Plasmodium falciparum
,”
Science
244 (1989): 1184â86; S. K. Martin, A. M. J. Oduola, and W. K. Mihous, “Reversal of Chloroquine Resistance in
Plasmodium falciparum
by Verapamil,”
Science
235 (1987): 899â901; C. C. Newbold, “The Path of Drug Resistance,”
Nature
345 (1990): 202â3; T. E. Wellems, L. J. Panton, I. Y. Gluzman, et al., “Chloroquine Resistance Not Linked to
mdr
-Like Genes in a
Plasmodium falciparum
Cross,”
Nature
345 (1990): 253â55; and S. J. Foote, D. E. Kyle, R. K. Martin, et al., “Several Alleles of the Multidrug-Resistance Gene Are Closely Linked to Chloroquine,”
Nature
345 (1990): 255â58.
187
Similar pumps are thought to exist in other parasites.
Entamoeba histolytica
, the gay bowel disease agent, appears to have acquired an
mdr
gene that is 35 percent identical to the malaria
mdr
. The parasite uses the pump to protect itself from the drug emetine. See J. Samuelson, P. Ayala, E. Orozco, and D. Wirth, “Emetine-Resistant Mutants of
Entamoeba histolytica
Overexpress mRNAs for Multidrug Resistance,”
Molecular and Biochemical Parasitology
38 (1990): 281â90.
Entamoeba histolytica
, the gay bowel disease agent, appears to have acquired an
mdr
gene that is 35 percent identical to the malaria
mdr
. The parasite uses the pump to protect itself from the drug emetine. See J. Samuelson, P. Ayala, E. Orozco, and D. Wirth, “Emetine-Resistant Mutants of
Entamoeba histolytica
Overexpress mRNAs for Multidrug Resistance,”
Molecular and Biochemical Parasitology
38 (1990): 281â90.
188
K. H. Riechmann, D. R. Davis, and D. C. Hutton, “
Plasmodium vivax
Resistance to Chloroquine?”
Lancet
II (1989): 1183â84.
Plasmodium vivax
Resistance to Chloroquine?”
Lancet
II (1989): 1183â84.
189
G. S. Murphy, H. Basri, Purnomo, et al., “
Vivax
Malaria Resistant to Treatment and Prophylaxis with Chloroquine,”
Lancet
341 (1993): 96â100.
Vivax
Malaria Resistant to Treatment and Prophylaxis with Chloroquine,”
Lancet
341 (1993): 96â100.
190
Ibid.
191
“Rediscovering Wormwood: Ginghaosu for Malaria,”
Lancet
339 (1992): 649â51; and E. Tanouye, “Chinese Tea Yields Secret of Its Success Against Malaria Bug,”
Wall Street Journal,
July 1, 1993: A1; Looareesuwan, Viravan, Vanijanonta, et al. (1992), op. cit.; and J. Karbwang, K. N. Bangchang, A. Thanavibul, et al., “Comparison of Oral Artemether and Mefloquine in Acute Uncomplicated
falciparum
Malaria,”
Lancet
340 (1992): 1245â48.
Lancet
339 (1992): 649â51; and E. Tanouye, “Chinese Tea Yields Secret of Its Success Against Malaria Bug,”
Wall Street Journal,
July 1, 1993: A1; Looareesuwan, Viravan, Vanijanonta, et al. (1992), op. cit.; and J. Karbwang, K. N. Bangchang, A. Thanavibul, et al., “Comparison of Oral Artemether and Mefloquine in Acute Uncomplicated
falciparum
Malaria,”
Lancet
340 (1992): 1245â48.
192
F. Gay, L. Ciceron, M. Litaudon, et al., “In-Vitro Resistance of
Plasmodium falciparum
to Qinghaosu Derivatives in West Africa,”
Lancet
343 (1994): 850â51.
Plasmodium falciparum
to Qinghaosu Derivatives in West Africa,”
Lancet
343 (1994): 850â51.
193
Sharma and Kondrashin, eds. (1991), op. cit.
194
See, for example, World Health Organization, “Global Malaria Control Strategy,” Ministerial Conference on Malaria, Amsterdam, October 26â27, 1992; and W. Rooney and K. Thimasarn, “Development of Multi-Drug Resistance in Forest Related
falciparum
Malaria,” in Sharma and Kondrashin, eds. (1991), op. cit.
falciparum
Malaria,” in Sharma and Kondrashin, eds. (1991), op. cit.
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