Imported malaria often severe among people with HIV

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French investigators have provided a description of the growing phenomenon of imported malaria among people with HIV. The report, published in the September 1st issue of the Journal of Immune Deficiency Syndromes, highlights that while treatment is generally successful, over a third of cases are severe. Prevention, they suggest, might be the best treatment for the disease.

Malaria is a significant health concern in many parts of the world. An estimated 350 – 500 million cases occur annually. International travel is making malaria a growing health issue in countries where the disease is not normally endemic, such as Western Europe or North America. France has seen a rise in cases of imported malaria over the previous decade, from 5109 cases in 1996 to 6392 in 2003.

Little is known of the origins, severity or treatment success of cases of imported malaria among HIV-positive people coming or returning to countries where the disease is not endemic. Such information could have value in determining how to prevent and treat the infection. Malaria is the most common fatal infection in returning travellers.

Glossary

malaria

A serious disease caused by a parasite that commonly infects a certain type of mosquito which feeds on humans. People who get malaria are typically very sick with high fevers, shaking chills, and flu-like illness. 

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

bilirubin

A substance produced during the normal breakdown of red blood cells. Bilirubin passes through the liver and is excreted in faeces. Elevated levels of bilirubin (jaundice) may indicate liver damage or disease.

plasma

The fluid portion of the blood.

The French Hospital Database on HIV (FHDH), established in 1992, is a prospective cohort of HIV-positive patients at 62 hospitals in France. Investigators culled database records from 1996 to 2003 for cases of malaria that were acquired in an endemic country and treated in France. They extracted data on type and severity of infection, origin of infection and history of treatment, as well as clinical data related to HIV infection.

Of the 190 identified cases, 178 (94%) were caused by Plasmodium falciparum, one of the most common types of malaria and the most deadly. All cases were among people returning from countries in sub-Saharan Africa, and half were from areas with a high prevalence of resistance to chloroquine, a cheap and effective anti-malaria drug that has become obsolete due to widespread resistance.

Preventative therapy was uncommon among the group. “Prescribed malaria chemoprophylaxis was appropriate in 44 cases (23%), but only 20 of these patients reported good adherence,” the investigators write.

Treatment of disease was successful in over 80% of cases. A small number of patients, 18 (10%), required intensive care, and complications occurred in 36 (20%) of cases. There was one death, in a patient with concomitant malaria and pneumonia.

While outcome was generally positive, just over one third of cases, 65 of 190, were initially classified as severe according to WHO criteria. Severe disease was associated with exhaustion and weakness, high blood levels of bilirubin and acid, kidney failure and the infection of the blood vessels supplying the brain. There is some evidence that from malaria-endemic countries that HIV infection is linked to higher rates of severe malaria, but there is little information from countries with imported malaria.

Investigators then analysed the data for factors associated with increased risk of sever malaria. CD4 cell count less than 350 cells/mm3 was associated with a 2.58-fold higher risk of severe malaria than a higher CD4 count. Studies from Africa have seen a similar link, and the authors write, “Our study is the first to show an association between low CD4 cell counts and the severity of imported P. falciparum malaria in HIV-1–infected adult patients in a nonendemic industrialized country.”

Being female and coming from a country with high prevalence of chemoresistance were protective against severe cases of the disease. Multivariate analysis found that age, HIV plasma viral load levels, being a native of sub-Saharan Africa and antiretroviral use were not associated with severe cases of the disease.

Given the high proportion of severe cases, prevention may be the best treatment for imported malaria. “All travelers,” the investigators conclude, “and especially HIV-1–infected patients departing for endemic countries, should systematically receive counseling and antimalarial chemoprophylaxis to reduce the risk and the severity of acute malaria whatever be their country of destination.”

References

Mouala C et al. Imported malaria in HIV-infected patients enrolled in the ANRS CO4 FHDH study. J Acquir Immune Defic Syndr 49:55 – 60, 2008.