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Co-infections: a neglected research priority

14 Aug 2008

Mzamose Gondwe

Source: Parasitology (see original article)

Infection with multiple parasites is increasingly being observed in the tropics however there is very little research activity on its impact on public health. The journal, Parasitology, dedicated their June issue to addressing important questions on co-infection; an area, which despite increased research activity, is still underdeveloped. Three papers in the co-infection special issue highlight the lack of evidence on the interaction between helminth and malaria co-infection and HIV and helminth co-infection.

Nacher is able to show from studies done in Thailand on helminth and malaria co-infections that worms protect themselves by protecting the host from severe malaria (1). He describes studies that show people infected with helminths are less likely to have cerebral malaria (2,3), renal failure (4,5), or high fever (6) compared to those infected with helminths. Anemia (7), gametocyte carriage (8), mixed plasmodial infections (9) are more prevalent in helminth-infected patients. A study in Thailand shows P falciparum malaria incidence (10) increases two-fold in helminth infected patients however studies done elsewhere (11,12) on clinical and immunological aspects of malaria incidence and helminth infections contradict these findings. Further studies are needed to clarify malaria incidence and severity with helminth co-infection.

A review by Pullan and Brooker describes field studies on the nutritional and pathological consequences of multiple infections with Plasmodium and helminths (13). They focus on soil-transmitted helminth infections (STH: Ascaris

lumbricoides, Trichuris trichiura and hookworm), schistosomiasis (Schistosoma haematobium, S. mansoni and S. japonicum) and Plasmodium spp. Multiple species infection may have an additive or multiplicative impact on growth in children (14), can cause micronutrient deficiencies (15), and can have synergistic effects on organ pathology (16). The authors state scientific understanding of co-infection is inadequate and well-designed intervention studies are needed to elucidate the health impacts of co-infections. They argue that a better understanding of co-infections is crucial to the rational design of public health control programmes.

Lloyd-Smith, Poss and Grenfell discuss how new strains of parasites may emerge as a result of alterations in immune status when HIV infected (17). Similar interactions are known to occur between HIV-1 and Mycobacterium tuberculosis (18), Leishmania (19), and malaria (20). They focus on clinical and epidemiological evidence from five parasite diseases (malaria, leishmaniasis, schistosomiasis, trypanosomiasis, and strongyloidiasis) with emphasis on HIV co-infection influencing transmission dynamics and efficacy of drug treatments. A mathematical model is proposed that investigates how individual-level properties may impact at a population-level. The authors demonstrate that HIV-1 co-infection can led to the emergence of new strains of parasites but further research is needed.

References

1. Nacher M (2008). Worms and malaria: blind men feeling the elephant? Parasitology;135(7):861-868. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18377695

2. Nacher M, Gay F, Singhasivanon P et al (2000). Ascaris lumbricoides is associated with protection from cerebral malaria. Parasite Immunology; 22: 107–113. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10672191

3. Nacher M, Singhasivanon S, Traore B et al. (2002). Helminth infections are associated with protection from cerebral malaria and increased nitrogen derivatives concentrations in Thailand. American Journal of Tropical Medicine and Hygiene; 66: 304–309. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12139225

4. Nacher M, Singhasivanon P, Silamchamroon et al (2001). Helminth infections are associated from protection from malaria related acute renal failure and jaundice in Thailand. American Journal of Tropical Medicine and Hygiene; 65: 834–836. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11791982

5. Nacher M, Treeprasertsuk S, Singhasivanon P, et al (2001). Association of hepatomegaly and jaundice with acute renal failure but not with cerebral malaria in severe falciparum malaria in Thailand. American Journal of Tropical Medicine and Hygiene; 65: 828–833. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11791981

6. Nacher M, Singhasivanon P, Traore B, et al (2001). Hookworm infection is associated with decreased body temperature during mild Plasmodium falciparum malaria. American Journal of Tropical Medicine and Hygiene; 65: 136–137. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11508388

7. Nacher M, Singhasivanon P, Gay F et al (2001). Helminth infections are associated with decreased reticulocyte counts and hemoglobin concentration in Thai-falciparum malaria. American Journal of Tropical Medicine and Hygiene; 65: 335–337. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11693879

8 Nacher M, Singhasivanon P, Silachamroon U et al (2001). Helminth infections are associated with increased gametocyte carriage during mild falciparum malaria in Thailand. American Journal of Tropical Medicine and Hygiene; 65: 644–647. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11716129

9. Nacher M, Singhasivanon P, Gay F et al(2001). Contemporaneous and successive mixed Plasmodium falciparum and Plasmodium vivax infections are associated with Ascaris lumbricoides : an immunomodulating effect? Journal of Parasitology; 87: 912–915. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11534659

10. Nacher M, Singhasivanon P, Yimsamran S et (2002). Intestinal helminth infections are associated with increased incidence of Plasmodium falciparum malaria in Thailand. Journal of Parasitology; 88: 55–58. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12053980

11. Murray MJ, Murray AB, Murray MB et al (1977). Parotid enlargement, forehead edema, and suppression of malaria as nutritional consequences of ascariasis. American Journal of Clinical Nutrition; 30: 2117–2121. Available from: http://www.ncbi.nlm.nih.gov/pubmed/930882

12. Lyke KE, Dicko A, DaboA et al (2005). Association of Schistosoma haematobium infection with protection against acute Plasmodium falciparum malaria in Malian children. American Journal of Tropical Medicine and Hygiene; 73: 1124–1130. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16354824

13. Pullan R, Brooker S. (2008) The health impact of polyparasitism in humans: are we under-estimating the burden of parasitic diseases? Parasitology; 135(7):783-794. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18371242

14. Stephenson LS, Latham MC, Ottesen EA (2000). Malnutrition and parasitic helminth infections. Parasitology; 121 (Suppl): S23–S38. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11386688

15 Friedman JF, Kanzaria HK, McGarvey ST (2005). Human schistosomiasis and anemia: the relationship and potential mechanisms. Trends in Parasitology; 21: 386–392. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15967725

16. Booth M, Vennervald BJ, Kenty L et al (2004). Micro-geographical variation in exposure to Schistosoma mansoni and malaria, and exacerbation of splenomegaly in Kenyan school-aged children. BMC Infectious Diseases; 4: 13. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15147584

17. Lloyd-Smith JO, Poss M, Grenfell BT. (2008) HIV-1/parasite co-infection and the emergence of new parasite strains. Parasitology;135(7):795-806. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18371236

18 . Williams BG, Dye C. (2003). Antiretroviral drugs for tuberculosis control in the era of HIV/AIDS. Science; 301: 1535–1537. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12920302

19. Desjeux P, Alvar J (2003). Leishmania/HIV co-infections : epidemiology in Europe. Annals of Tropical Medicine and Parasitology; 97: 3–15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14678629

20. Whitworth J, Morgen D, Quigley M et al (2000). Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study. Lancet; 356: 1051–1056. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11009139

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