Does HIV infection affect cure rates after treatment for schistosomiasis?

Treatment of schistosomiasis with the drug praziquantel (Cysticide) may be ineffective in patients with HIV infection, according to a study from Zimbabwe published in the 15th June edition of Clinical Infectious Diseases. The study found that the drug can reduce the number of eggs produced by the worms, but that it may not kill the worms themselves.

Schistosomiasis or ‘bilharzia’ is a disease caused by parasitic worms, which is common in tropical countries. The worms or ‘schistosomes’ have complex life-cycles including a stage that infects pond snails. These release offspring that can infect humans by burrowing through the skin, where they migrate to blood vessels. Here, they mature into adult worms and release eggs back into watercourses via the faeces or urine.

A number of studies have examined the interactions between schistosomiasis and HIV, finding that the standard treatment of a single dose of praziquantel is as effective in patients with and without HIV. However, these studies have generally examined the effect of the drug on the numbers of eggs found in the faeces or urine.

Praziquantel works by disrupting the worms’ protective covering, exposing them to the human immune system. Animal studies have suggested that individuals with impaired immune systems are less successful in clearing the worms from the body, raising the possibility that the drug may simply reduce the number of eggs produced by the worms, rather than killing the adult worms themselves.

To investigate this possibility, researchers examined the schistosomiasis cure rates in 142 patients in Zimbabwe after a dose of 40 mg/kg praziquantel. Eighty of the patients were HIV-positive and 62 were HIV-negative, but equal proportions of each group were free of eggs three months after treatment (86 vs. 85%; p = 0.57). The change in number of eggs in each patient was also similar between HIV-positive and –negative groups (p = 0.35).

However, the investigators also measured the levels of ‘circulating anodic antigen’ (CAA) in the blood of 187 patients. CAA is a chemical released by the worms that is a marker of active infection, with values below 40 pg/ml indicating cure.

Cure rates based on CAA levels were lower than those from egg counts. However, they revealed that the 108 HIV-positive patients had lower cure rates than the 79 HIV-negative patients (31 vs. 52%; p

The investigators offer a number of explanations for this discrepancy, including the possibility of infection with juvenile worms that are insensitive to praziquantel, persistence of CAA in the blood or re-infection with schistosomes in HIV-positive patients. However, the most likely explanation is that praziquantel requires a strong immune system to clear worms from the body, and simply reduces the number of eggs released by the worms in patients with HIV.

“The effect of praziquantel may be limited to affecting the fecundity of adult schistosomes in the immunocompromised host, thus reducing egg excretion while leaving schistosomes metabolically active”, they conclude. “The findings of the present study raise concern as to the function and efficacy of praziquantel for the immunocompromised HIV-infected individual.”

There were no differences in the responses of patients with CD4 cell counts above and below 200 cells/mm³. Response rates were also similar between patients infected with Schistosoma mansoni, whose eggs are found in the faeces, and S. haematobium, which releases its eggs into the urine.

Although further studies are needed to confirm the investigators' hypothesis, they suggest that previous studies using egg counts may have over-estimated the effect of treatments for schistosomiasis in HIV-positive patients. In addition, the persistence of worms in the body after treatment may lead to increased HIV levels and disease progression.

“It may be necessary to develop and implement different schistosomiasis treatment guidelines for HIV-positive subjects that involve either repeated treatment and / or higher doses of praziquantel,” they conclude.