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To find out whether malaria occurred at an increased frequency in HIV-infected individuals and to evaluate the clinical course and risk factors for malarial infection in HIV, a prospective study was carried out in a tertiary care centre from June, 1999 to December, 2000 among HIV-infected individuals with HIV-uninfected individuals taken as control.
In this study, out of 250 individuals, 152 were HIV-infected and the remaining were HIV-negative. The odd’s ratio (OR) for the occurrence of malaria in the HIV-infected population compared with the HIV-uninfected population was 2.5 (95% confidence interval: 1.01, 6.4; p<0.02). The prevalence of malaria in HIV infection was 20.4%. The same was 8.3% in asymptomatic stage, and 22.6 % and 21.3% in the early and late symptomatic stages of HIV disease respectively. Among those who came for follow-up 44.4% of the HIV-infected individuals had recurrence of malarial infection. Contrary to what was thought before, malaria occurred at an increased frequency in HIV cases. The occurrence of malaria increased in the symptomatic stages of HIV disease compared to the asymptomatic stage. Recurrence was high in the HIV-infected population. [J Indian Med Assoc 2007; 105: 82-4 & 87]
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Key words : Malaria, HIV, AIDS, coinfection, risk factors.
Malaria was one of the few diseases, which was thought to have clinical course that was unaltered by
HIV infection1. There was a case report2 of cerebral malaria associated with HIV infection. Other earlier studies3,4 demonstrated little evidence that malaria occurred at increased frequency in HIV infection.
In this part of the world where malaria is endemic, many HIV-infected individuals were infected with malarial. This study was conducted to find out whether malaria occurred at an increased frequency in the HIV-infected population compared to the HIV-uninfected population. The clinical course and risk factors for malaria in HIV infection were also evaluated.
Material and Method
HIV-infected and-uninfected individuals admitted as inpatients in the Institute of Sexually Transmitted Diseases, Government General Hospital, Chennai, and who had symptoms and signs suggestive of malarial infection were screened for malarial parasites. Malarial infection was confirmed by peripheral smear or by quick buffer coating test. Enzyme-linked immunosorbant assay (ELISA) for HIV 1 and 2 were done for all the individuals enrolled in this study. HIV infection was confirmed either by westernblot assay or by double ELISA using two different antigen kits. ELISA negative individuals who did not have a history of unprotected sexual exposure in the previous six months were enrolled in the HIV-uninfected group. ELISA negative individuals with the above sexual history were either excluded from the study or included in the HIV-uninfected group, if their repeat ELISA that was done after six months from the last sexual exposure was negative.
The individuals with malarial infection were followed-up till the end point of the study. During the follow-up, the occurrence of recurrent malaria was noted. ELISA negative individuals who came for follow-up were subjected to repeat ELISA at intervals of six months.
The HIV-infected individuals were evaluated for the presence of splenomegaly, anaemia, persistent generalised lymphadenopathy and opportunistic infections. They were categorised into asymptomatic, and early and late symptomatic stages of HIV disease, depending upon their clinical features and CD4 cell counts. Asymptomatic stage of HIV disease included individuals with a CD4 count of more than 500 cells/cmm and did not have opportunistic infections. Early symptomatic stage included those with CD4 counts between 200 and 500 cells/cmm and had opportunistic infections as well as other manifestations, which were not included as AIDS indicator illnesses by the Centers for Disease Control and Prevention, Atlanta (CDC)5. Late symptomatic stage illnesses by the Centers for Disease Control and Prevention, Atlanta (CDC)5. Late symptomatic stage included individuals with CD4 counts of less than 200 cells/cmm and/or had diseases included as AIDS indicator illnesses by CDC5.
Odd’s ratio (OR) and 95% confidence intervals (CI) were calculated. P-value was calculated using the Pearson’s chi-square statistics.
Observations
A total of 250 individuals were enrolled in this study. There were 152 individuals who were HIV-infected and the remaining were HIV-uninfected. The average age of the HIV-infected individuals was 29.4 years (range: 16-50 years) and that for the HIV-uninfected population was 25.8 years (range: 15-42 years). Among the HIV-infected population 131 were males, 17 were females and 4 were trans-sexuals. In the HIV-uninfected group 72 were males and the remaining were females. Thirty-one of the 152 HIV-infected individuals and 9 of the 98 HIV-uninfected individuals had malaria. The prevalence of malaria was 20.4% in the HIV-infected population and 9.2% in the HIV-uninfected population. The OR for the occurrence of malaria in the HIV-infected group was 2.5 (95%CI: 1.01, 6.4; p<0.02) compared to that in the HIV-uninfected group.
Of the 31 HIV-infected individuals with malaria, only 9 came for follow-up. Among them, 4 (44.4%) had recurrence of malaria (average duration of follow-up was 2.8 months; range: 1-8 months). In the HIV-uninfected group, 5 came for follow-up and none of them had recurrence of malaria. The p-value for the occurrence of recurrent malarial infection in the HIV-infected group compared to that of the HIV-uninfected group was less than 0.01. The average duration for the recurrence of malaria in the HIV infected group was 3.75 months (range: 1-8 months). Recurrent episodes of malaria were caused by the same species of plasmodium that caused the initial episode. Two individuals with recurrent malaria had P falciparum and the other two had P vivax.
The prevalence of malaria in various stages of HIV was, 8.3% in asymptomatic, 22.6% in early symptomatic, and 21.3% in late symptomatic stages of HIV infection.
The OR for various risk factors for malarial infection in HIV was 1.83 for splenomegaly, 1.56 for anaemia, 1.28 for oropharyngeal candidiasis, and 2.05 for persistent generalised lymphadenopathy (PGL) (Table 1).
Discussion
In this study the prevalence of malaria in the HIV-infected population was 20.4% compared to a prevalence of 9.2% in the HIV-uninfected population (p<0.02). Earlier studies3,4,6 did not report an increase in the prevalence of malaria among HIV-infected individuals. Most of the earlier studies did not have a control group. Some were done in non-endemic areas for malaria. The exact pathogenesis of susceptibility of HIV-infected individuals to malaria was not clear. Whether this susceptibility was due to an immunological background or other factors was not known.
Malaria was observed at an increased frequency in the symptomatic stages of HIV disease. Whether HIV-infected individuals were infected with malaria at an early stage (asymptomatic period) and manifested at a later stage (symptoamatic period) due to immunosuppression, or the individuals in symptomatic stage of disease were more susceptible to fresh infection by malarial parasite was not known. Earlier studies did not reveal an increase in malarial infection in the later stages of HIV disease1. The effect of malaria coexisting with HIV was not well understood, while the effects of coexisting sexually transmitted infections on HIV were reported7.
One study8 conducted by earlier researchers did not report an altered clinical course of malaria in HIV infection. There was a case report2 of severe cerebral malaria associated with HIV infection. In the present study it was observed that the recurrence of malaria was high in the HIV-infected population compared to the HIV-uninfected group (p<0.01). Other earlier studies did not observe this finding as many of them were conducted on subjects from non-endemic areas who had travelled to endemic areas only for a short period. The chances for reinfection in these individuals were minimal, 50% of the recurrence was due to P falciparum infection. It was not known whether these recurrences were as a result of reinfection due to an altered immune status or as a result of resistance to primary drugs for malaria. If it was due to a drug-resistant strain, whether HIV-infected individuals were more susceptible to such strains or, these strains became drug-resistant due to coinfection with HIV, was to be answered. Both could pose serious health hazards to the society.
In this study the average duration for first recurrent episode of malaria was 3.75 months. Whether this duration shortened with the progression of HIV disease had to be evaluated by involving larger number of malaria and HIV coinfected individuals. HIV-infected individuals with splenomegaly and anaemia had a greater chance of having malaria as coinfection (OR=1.83 and 1.56 respectively). Malaria could be a cause for splenomegaly and anaemia. Whether splenomegaly and anaemia could be taken, as an index for diagnosing malaria in HIV infection needed further evaluation. The fact that malaria was more frequently associated with oropharyngeal candidiasis and PGL (OR=1.28 and 2.05 respectively) indicated that a suppressed but functioning immune system was essential for malarial coinfection in HIV.
To conclude, malaria occurred at an increased frequency in HIV infection with an increased chance of recurrence. The occurrence of malaria increased in the symptomatic stages of HIV disease.
References
1 Bollinger RC, Quinn TC — Tropical diseases in the HIV-infected traveller. In: Broder S, Merigan T, Bolognesi D, editors. Textbook of AIDS Medicine. Baltimore: Williams and Wilkins, 1994: 311-22.
2 Miskovits E, Banhegyi D, Axmann A, Vjhelyi E, Illey G, Varnai F — Severe Cerebral Malaria Association with HIV Infection [Abstract 5547]: Fourth International Conference on AIDS, Stockholm, Sweden, June 1988. Stockholm: ICAIDS, 1988.
3 Greenberg AE, Nguyen-Dinh P, Mann JM, Kobote N, Colebunders RL, Francis H, et al — The association between malaria, blood transfusions, and HIV seropositivity in a pediatric population in Kinshasa, Zaire. JAMA 1988; 259: 545-9.
4 Nguyen-Dinh P, Geenberg AE, Mann JM, Kabote N, Francis H, Colebunders RL, et al — Absence of association between Plasmodium falciparum malaria and human immunodeficiency virus infection in children in Kinshasa, Zaire. Bul World Health Organ 1987; 65: 607-13.
5 Centers for Disease Control and Prevention — 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adults and adolescents. MMWR CDC Surveill Summ 1992; 41: RR-17.
6 Ruff TA — Travellers with HIV. In: Stewart G, editor. Managing HIV infection. North Sydney: Australian Medical Publishing Company Limited, 1997: 146-8.
7 Muthu M, Sampath Kumaar G, Balasubramaniam MP — Estimation of Median time interval between the occurrence of STI and the occurrence of AIDS indicator illnesses in HIV-infected individuals [Abstract 0066]: Sixth International Congress on AIDS in Asia and the Pacific, Melbourne, Australia, October 2001. Melbourne: ICAIDSAP, 2001.
8 Steffen R, Rickenbach M, Wilhelm U, Helminger A, Schar M — Health problems after travel to developing countries. J Infect Dis 1987; 156: 84-91.
*MD (STD), Dip NB (Dermatol and Venereol), Consultant in HIV/AIDS/STI, Rajan Hospital, Madurai 625010
**MD, DV, Professor and Head of the Department of STD,Chengalpattu Medical College, Chengalpattu 603001
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