Malaria diagnosis and hospitalization trends, Brazil.

We focused on rates of malaria in the state of Amazonas and city of Manaus, Brazil. Plasmodium vivax accounted for an increased number and rate of hospital admissions, while P. falciparum cases decreased. Our observations on malaria epidemiology suggest that the increased hospitalization rate could be due to increased severity of P. vivax infections.

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The study of malaria prevalence in the state of Amazonas and city of Manaus indicates an increase in the percentage of hospitalized Plasmodium vivax patients and an overall increase in malaria cases caused by this parasite. Our observations on malaria epidemiology and case treatment suggest that the increased hospital admissions are associated with a higher frequency of severe disease associated with P. vivax infections. Amazonas includes most of the Brazilian Amazon Region, where malaria has been controlled but never eradicated. Since the 1980s, there has been a reemergence of malaria, which appears to coincide with changing malaria control policies associated with the ending of the Malaria Eradication Campaign (1,2).

From January through August 2003, the number of cases nationwide was reduced by 2.6%, when compared with the same period in 2002. However, this change did not represent a uniform reduction in the number of malaria infections within the country. The states of Amazonas, Rondonia, and Tocantins reported increases of 82.9%, 14.7%, and 10.3%, respectively (3). Perhaps the best indicator of what has been occurring with malaria control during the past 5 years is reflected in recent statistics for malaria in Amazonas and the city of Manaus. During 2002 and 2003, the number of malaria cases reported in Amazonas increased 103.3% (4).

An observational study conducted in the reference center for diagnosis and treatment of malaria in Amazonas (Fundacao de Medicina Tropical do Amazonas [FMT-AM]) described severe disease, including thrombocytopenia with hemorrhagic manifestations during infection with P. vivax. In that series, 46 (61.3%) of 75 patients admitted to the hospital for treatment of P. vivax malaria were classified with severe disease using predetermined criteria (5). We considered increased case severity as the need to hospitalize patients for treatment. Our primary goals were to present the epidemiology of malaria in Amazonas and the city of Manaus from 1980 to 2006 and to describe the overall rates, prevalence, and admission rates of malaria caused by P. falciparum and P. vivax.

The Study

We extracted total yearly cases of malaria and population size in Amazonas from the database maintained by the Brazilian Ministry of Health (DATASUS, 2004), National Foundation of Health (6-8), and Secretary of Surveillance in Health (3,9). Data from FMT-AM were extracted from the malaria logbooks (for the years before the Foundation started publishing the reports) and from the Quarterly reports (for the years that the Foundation published the reports). All malaria cases diagnosed and referred for treatment are maintained (1989-1994) and quarterly reports are published by the FMT-AM (10). Quarterly reports published from 1995 to 2004 provided the total number of malaria diagnoses, case-patients admitted to the hospital, and number of deaths. Data from 2005 and 2006 were obtained by one of the authors (M.R.F. Costa) directly at FMT-AM (Subgerencia de Arquivos Medicos e Contas Hospitalares). The hospital protocol is to exclude mixed infections by additional testing. We collected and tabulated data from these sources by year, parasite species, admissions, and percent admissions (Table). Percent admission was calculated as the total number of case-patients admitted to the hospital due to the specified parasite, divided by the total number of malaria cases caused by that same parasite in FMT-AM during that year, multiplied by 100.

Malaria cases from all causes in Amazonas, 1980-2006, are presented in Figure I. An irregular increase is noted since 1988, reaching a peak in 1999, followed by a decline in 2001, only to rise again in the following years. A decrease was observed in 2006, but the data are not final. Figure 1 also shows the total number of malaria cases diagnosed at FMT-AM; fluctuations observed are very similar in direction and relative magnitude to those found statewide.

The number of infections due to P. falciparum and P. vivax diagnosed annually at FMT-AM are shown in Figure 2, panel A. The percentage of diagnosed case-patients admitted to the hospital, by parasite and year, is presented in Figure 2, panel B. In 1989, 264 (20%) of the patients with a diagnosis of P. falciparum infection were admitted to the hospital, while only 26 (0.85%) of those infected with P. vivax required admission. While P. falciparum remains the main cause of malaria admissions, we observed a significant increase in P. vivax admissions: the mean percent admissions from 1989 to 1996 was 0.59% (standard deviation [SD] 0.18), increasing to 1.91% (SD 0.74) from 1997 to 2006. This relative increase in P. vivax malaria requiring admission to the hospital for treatment was disproportionate to the change in numbers of cases and to the relative frequency of P. vivax cases over P. falciparum malaria cases.

Conclusions

We presented the epidemiology of recent malaria cases in the State of Amazonas and city of Manaus, emphasizing the emergence of severe P. vivax malaria. Assuming that patients requiring hospital admission were sicker than those treated as outpatients, we observed that malaria transmission in this region was continuous and fluctuated in intensity. P. vivax was consistently the main cause of malaria, but the number of patients with P. vivax requiring hospital admission increased significantly in recent years. Changes in control operations were linked to the reestablishment of malaria in major urban areas of the Amazon basin, e.g., Belem (11). In Manaus, this could have had an impact on P. vivax disease manifestations and severity but did not seem to have affected the severity of disease caused by P. falciparum, perhaps because the current policy of early diagnosis and treatment has been reported to have a greater impact on disease caused by P. falciparum than P. vivax (12,13).

In this study, we assumed that case definition and criteria for admission at FMT-AM, for both P. vivax and P. falciparum malaria, were relatively constant (http://www. fmt.am.gov.br/). Our data showed that the likelihood of hospital admissions for case-patients diagnosed with P. vivax malaria increased substantially after 1996, while the percentage of P. falciparum admissions declined. The decreasing rate of admission for P. falciparum malaria during the later years of our study supports the interpretation that the criteria for admission to FMT-AM were not loosened. It is possible that referrals to FMT-AM from elsewhere in the region increased during this period, but that would likely affect P. falciparum admissions too. Based on these considerations, we interpret the data as suggestive of an increased illness associated with P. vivax infections in the region.

[FIGURE 1 OMITTED]

In this study we did not attempt to describe the specific disease manifestations that were the basis for admissions of individual patients. However, recent reports described a range of unusual manifestations of P. vivax infection elsewhere (14), consistent with the disease manifestations reported in Manaus (5).

Biologic aspects of the human host, vector, and parasite and changes in the environment contribute to the epidemiology of malaria. Our data demonstrate that malaria is a growing health burden in the Amazon Region of Brazil and that disease caused by P. vivax is a substantial and increasing threat to the health of the population in Manaus. More studies are needed to understand the complex mechanisms of this disease and its impact on susceptible populations.

[FIGURE 2 OMITTED]

This research was supported in part by National Institutes of Health grants U01 AI054777 and R01 AI49726.

References

(1.) Brazil: Ministerio da Saude, Fundacao Nacional de Saude (FU-NASA). Vigilancia Epidemiologica: Programa Nacional de Prevencao e Controle da Malaria-PNCM. Brasilia-DF. Dec 2002. [cited 2007 Aug 29]. Available from http://www.funasa.gov.br

(2.) Loiola CCP, da Silva CJM, Tauil PL. Controle da malaria no Brasil: 1965-2001. Rev Panam Salud Publica. 2002;11:235-44.

(3.) Brasil, Ministerio da Saude, Secretaria de Vigilancia em Saude (SVS). Boletim Epidemiologico da Malaria. No. 2. Dec 2003. [cited 2007 Aug 29]. Available from http://dtr2001.saude.gov.br/svs/epi/ malaria/pdfs/be_malaria_02_2003.pdf

(4.) Fundacao de Medicina Tropical do Amazonas (FMT-AM), 2005. Informe Epidemiologico, No. 1. 2005. Malaria notificada no Amazonas no Periodo de 2003 a 2004.

(5.) Alecrim MGC. Estudo Clinico, resistencia e polimorfismo parasitario na malaria pelo Plasmodium vivax, em Manaus. Brasilia-DF: 2000. Universidade de Brasilia; Faculdade de Medicina/Nucleo de Medicina Tropical, Tese de Doutorado. p. 177.

(6.) Brazil: Fundacao Nacional de Saude (FUNASA). Vigilancia Epidemiologica: Situacao da Prevencao e Controle das Doencas Transmissiveis no Brasil. Brasilia-DF. Sep 2002:22-3. [cited 2007 Aug 29]. Available from http://www.funasa.gov.br

(7.) Brazil: Fundacao Nacional de Saude (FUNASA). Vigilancia Epidemiologica. Brasilia-DF. 2004. [cited 2007 Aug 29]. Available from http://www.funasa.gov.br

(8.) Brasil: Fundacao Nacional de Saude (FUNASA). Vigilancia Epidemiologica: Casos confirmados, segundo o periodo de diagnostico e local de residencia, por U.F. Brasil, 1980-2001. Brazil-DF. 2003. [cited 2007 Aug 29]. Available from http://www.funasa.gov.br

(9.) Brasil: Secretaria de Vigilancia em Saude (SVS). Serie historica de casos de Doencas de Notificacao compulsoria-Amazonas, 1980-2001. Brasilia-DF. 2004. [cited 2007 Aug 29]. Available from http:// dtr2001.saude.gov.br/svs/epi/situacaodoencas/transmissiveis00.htm

(10.) Fundacao de Medicina Tropical do Amazonas (FMT-AM). Boletim trimestral, Numeros 1 a X. Manaus, Amazonas, Brasil: 1995 to 2004.

(11.) Libonati RM, Dos Santos MVN, Pinto AYN, Calvosa AM, Ventura PHM, Figueiredo JM, et al. Malaria autoctone na Grande Belem: panorama atual e prevalencia no ultimos seis anos. Rev Soc Bras Med Trop. 2000;33(Suppl 1):347.

(12.) Mendis K, Sina BJ, Marchesini P, Carter R. The neglected burden of Plasmodium vivax malaria. Am J Trop Med Hyg. 2001;64:97-106.

(13.) Pan American Health Organization. Situation of malaria programs in the Americas. Epidemiol Bull/PAHO. 2001;22:10-4.

(14.) Kochar DK, Saxena V, Singh N, Kochar SK, Kumar SV, Das A. Plasmodium vivax malaria. Emerg Infect Dis. 2005;11:132-4.

Patricia D. Santos-Ciminera, * ([dagger]) Donald R. Roberts, * Maria das Gracas C. Alecrim, ([dagger]) Monica R.F. Costa, ([dagger]) and Gerald V. Quinnan Jr *

* Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA; and ([dagger]) Fundacao de Medicina Tropical do Amazonas, Manaus, Brazil

Address for correspondence: Patricia D. Santos-Ciminera, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Room A3079, Bethesda, MD 20814, USA; email: [e-mail]

Dr Santos-Ciminera is originally from Brazil, where she worked at the Foundation of Tropical Medicine of Amazonas. She is currently an adjunct professor at Villa Julie College in Maryland. Her primary research interests are malaria epidemiology (traditional and molecular) and pathogenic mechanisms of infectious diseases.

Table. Total malaria cases in the state of Amazonas, Brazil,
1980-2006, and malaria case-patients diagnosed and admitted
at FMT-AM by parasite, 1989-2006 *

                                       FMT-AM

                               Plasmodium falciparum

                    Malaria,                   No.
        Amazonas      all      No. case-    admitted
Year   ([dagger])    causes    patients         N

1980     4,447         --         --           --
1981     8,169         --         --           --
1982     13,142        --         --           --
1983     10,299        --         --           --
1984     8,528         --         --           --
1985     11,196        --         --           --
1986     15,319        --         --           --
1987     15,233        --         --           --
1988     19,392        --         --           --
1989     34,944      4,347       1,262     264 (20.92)
1990     28,479      3,037        839      175 (20.86)
1991     45,849      5,765        664      179 (26.96)
1992     37,885      5,083        670      118 (17.61)
1993     55,364      10,157      2,834     325 (11.47)
1994     68,287      7,469       1,433     199 (13.89)
1995     52,602      5,765       1,049     174 (15.08)
1996     70,044      6,206       1,333     201 (15.08)
1997     94,382      10,483      1,871     186 (9.78)
1998    114,748      10,854      1,751     217 (12.39)
1999    167,722      19,967      4,459     341 (7.65)
2000     96,026      12,266      2,541     177 (6.97)
2001     48,385      4,315        813      127 (15.62)
2002     70,223      88,711       992      106 (10.69)
2003    143,343      30,017      2,213     150 (6.78)
2004    152,440      27,169      5,727     257 (4.49)
2005    229,330      31,243      8,698     264 (3.52)
2006    190,378      16,182      3,363     175 (4.31)

                     FMT-AM

                                 Other causes
                                   ([double
                P. vivax           dagger])

                       No.
       No. case-    admitted      No. case-
Year   patients         N          patients

1980      --           --             --
1981      --           --             --
1982      --           --             --
1983      --           --             --
1984      --           --             --
1985      --           --             --
1986      --           --             --
1987      --           --             --
1988      --           --             --
1989     3,043      26 (0.85)         42
1990     2,175      15 (0.69)         23
1991     5,076      23 (0.45)         25
1992     4,398      29 (0.66)         15
1993     7,284      24 (0.33)         39
1994     5,948      44 (0.74)         88
1995     4,518      30 (0.66)        198
1996     4,686      18 (0.38)        187
1997     8,506     175 (2.06)        106
1998     9,004     116 (1.29)         99
1999    15,238     155 (1.02)        270
2000     9,227     147 (1.59)        498
2001     3,443      95 (2.76)         59
2002     7,808     263 (3.37)         71
2003    27,679     677 (2.45)        125
2004    21,228     345 (1.63)        214
2005    22,174     378 (1.70)        371
2006    12,672     161 (1.27)        147

* 2005-2006 data obtained at the Malaria Laboratory and
Epidemiology Department of the FMT-AM by M.R.F.C. FMT-AM,
Fundacao de Medicina Tropical do Amazonas; --, data not
available.

([dagger]) Total malaria cases in the state of Amazonas.

([double dagger]) Includes P. malariae infections and mixed
infections (P. falciparum + P. vivax).