Infect Immun. 2014 Jan;82(1):243-52.

Characteristic age distribution of Plasmodium vivax infections after malaria elimination on Aneityum Island, Vanuatu.

Kaneko A, Chaves LF, Taleo G, Kalkoa M, Isozumi R, Wickremasinghe R, Perlmann H, Takeo S, Tsuboi T, Tachibana S, Kimura M, Björkman A, Troye-Blomberg M, Tanabe K, Drakeley C.

Island Malaria Group, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

 

Abstract

Resurgence is a major concern after malaria elimination. After the initiation of the elimination program on Aneityum Island in 1991, microscopy showed that Plasmodium falciparum disappeared immediately, whereas P. vivax disappeared from 1996 onward, until P. vivax cases were reported in January 2002. By conducting malariometric surveys of the entire population of Aneityum, we investigated the age distribution of individuals with parasites during this epidemic in the context of antimalarial antibody levels and parasite antigen diversity. In July 2002, P. vivax infections were detected by microscopy in 22/759 individuals: 20/298 born after the beginning of the elimination program in 1991, 2/126 born between 1982 and 1991, and none of 335 born before 1982. PCR increased the number of infections detected to 77, distributed among all age groups. Prevalences were 12.1%, 16.7%, and 6.0%, respectively (P < 0.001). In November, a similar age pattern was found, but with fewer infections: 6/746 and 39/741 individuals were found to be infected by microscopy and PCR, respectively. The frequencies of antibody responses to P. vivax were significantly higher in individuals born before 1991 than in younger age groups and were similar to those on Malakula Island, an area of endemicity. Remarkably low antigen diversity (h, 0.15) of P. vivax infections was observed on Aneityum compared with the other islands (h, 0.89 to 1.0). A P. vivax resurgence was observed among children and teenagers on Aneityum, an age distribution similar to those before elimination and on islands where P. vivax is endemic, suggesting that in the absence of significant exposure, immunity may persist, limiting infection levels in adults. The limited parasite gene pool on islands may contribute to this protection.

PMID: 24166950

 

SUPPLEMENT:

Recently, the scaling up of malaria control efforts in endemic countries has shown some promising results. This has led to renewed interest in malaria elimination with 39 countries stating their commitment to achieve elimination. Since these countries are all positioned along the endemic margins, prevention of reinfection and resurgence is an integral component of any elimination campaign. In the Asia Pacific region, the unique challenge for elimination relates to the relatively high proportion of Plasmodium vivax infections. Islands provide natural ecological experiments with a great potential for intervention studies and have demonstrated some early successes of malaria elimination (5). Vanuatu consists of 68 islands in Southwest Pacific with a high linguistic diversity. Despite different waves of human colonization, unstable malaria transmission has continued probably since the first human settlement 4000 years ago. Aneityum, the southernmost island in Vanuatu, is located at the south-east edge of the malaria extension in the Pacific. To examine the feasibility of malaria elimination, an integrated control program, combining mass drug administration and vector control, was initiated on Aneityum in 1991. Eight years later, it was concluded that malaria can be eliminated from isolated islands if there is a high degree of community commitment. One major concern is the possible reintroduction of infection due to inter-island human movement. To our knowledge, Aneityum is the only island in recent times where malaria elimination has been successfully maintained for more than a decade. Thus, observations from Aneityum can offer important insights into concerns regarding loss of anti-malarial immunity following elimination and how this might impact disease burdens in potential resurgences. An epidemic of P. vivax on Aneityum in 2002 provided us with an opportunity to investigate the age patterns of newly detected infections in the context of population level antibody responses to P. vivax and parasite antigen diversity. Individuals born before elimination had considerably fewer episodes of parasitemia than those born after elimination. Our findings indicate that protective immunity against P. vivax infections persists for a long time, at least 10 years, after the initiation of malaria elimination and thus absence of exposure to recurrent infections.

 

Acknowledgements.

We thank the families in Vanuatu who participated in the study; James Yaviong and Sam Yamar for field surveys; Margareta Hagstedt for ELISA tests; Naoko Sakihama for genetic analyses; Mayumi Fukui, Ikuko Kusuda, and Isao Kimata for PCR tests; Tomomi Kuwana for study administration. This work (PI: A. K.) was supported by Swedish Research Council grants (2008-3097 and 2009-3233), Japan Society for Promotion of Science Grants (24390141, 22406008, Asia-Africa Science Platforms), Health Labour Sciences Research Grant and the Global COE Program at Nagasaki University. C. D. received grant support from the Wellcome Trust (091924). L. F. C. is funded by Program for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases at Nagasaki University. This work is dedicated to late Professor Peter Perlmann.

 

References

  1. Kaneko A, Taleo G, Kalkoa M, Yaviong J, Reeve PA, Ganczakowski M, Shirakawa C, Palmer K, Kobayakawa T, Björkman A. 1998. Malaria epidemiology, glucose 6-phosphate dehydrogenase deficiency and human settlement in the Vanuatu Archipelago. Acta Trop. 1998;70:285–302.
  2. Kaneko A, Taleo G, Kalkoa M, Yamar S, Kobayakawa T, Björkman A. Malaria eradication on islands. Lancet. 2000; 356:1560–1564.

 

Contact:
Akira Kaneko, MD, PhD
Professor
Karolinska Institutet
Island Malaria Group
Department of Microbiology,
Tumor and Cell Biology (MTC)
Nobels vägen 16
SE-17177 Stockholm
Sweden
Email: akira.kaneko@ki.se
Akira-Figure-1Figure 1. Age-specific prevalence profiles for P. vivax infections in July 2002 and IgG antibodies to P. vivax antigens in 1998 (bars) on residents of Aneityum island, where P. falciparum malaria transmission had been interrupted since 1991 and P. vivax since 1996. Red bars represent the numbers of P. vivax infections by both microscopy and PCR, and light blue bars those by only PCR. All microscope positives were PCR-positive. Dark blue bars represent seropositive rates for antibodies to P. vivax erythrocyte stage antigens and orange bars those for antibodies to P. vivax CSP recombinant proteins, either VK210 or VK247.

Akira-Figure-2

Figure 2. The Vanuatu archipelago: distribution of Pvmsp1 and Pvcsp haplotypes in P. vivax parasites on Aneityum island during the outbreak in 2002, a decade after beginning the malaria elimination program (n= 27 & 25 for Pvmsp1 & Pvcsp, respectively) and other islands with malaria transmission, Gaua (n= 33 & 20, in 1997), Santo (n= 34 & 32, in 1996, 1997, & 2001), Ambae (n= 22 & 11, in 2002), Malakula (n= 14 & 12, in 1998 & 2001), Pentecost (n= 20 & 14, in 1998 & 2000), and Tanna (n= 15 & 11, in 1999 & 2002). See Tables 1 & 2 for the detailed haplotype classifications for Pvmsp1 and Pvcsp, respectively. Parasite rates detected during the case-selection surveys on these islands are presented in the map. The lower inset map shows the location of Vanuatu in Oceania.

Akira-Figure-3Fig 3. Akira on Aneityum island, February 2014.

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