Parasitic worms are a widespread health problem in many tropical and sub-tropical countries. They generally cause chronic illness rather than deaths. They contribute to malnutrition and have an impact on the growth and learning abilities of children, who tend to be more heavily affected than adults. Among adults, they can cause anaemia and chronic fatigue. The economic impact of these conditions is enormous and a major contributor to the economic difficulties faced by many affected countries and regions.

The relationship between worms and HIV is still controversial. Some groups have found that treatment of worms can, by itself, reduce the viral load in people with HIV who are infected with them, to about the same extent as monotherapy with AZT (zidovudine, Retrovir). Others have been unable to replicate this effect. Nonetheless, treatment of worm infection may become very important in the future, if vaccination emerges as an effective control strategy, since the immune system of people who are infected with worms is chronically depressed in ways that may influence the response to HIV and other vaccines (Bentwich 2003).

Symptoms, diagnosis and treatment

Any general information resources on tropical medicine will describe helminth infections, their diagnosis and treatment. Since there is no evidence that people with HIV have added vulnerability or experience different symptoms they are not covered here, except to mention that the usual treatment is with drugs such as praziquantel (the main treatment for schistosomiasis and many other helminths), usually given as a single dose.

While some worms can occasionally give rise to major crises - for example, blockage of the intestines, requiring surgical intervention - diagnosis generally depends on microscopic examination of stools or urine samples to identify the eggs that are shed from them.

Treatment strategies are generally set at a population level, with widespread distribution of effective treatments at intervals of 3 to 6 months, for example, to all school children. There is still some controversy about the efficacy of these programmes. The bottom line seems to be, that children's literacy and other indicators of educational performance don't recover simply because they are given drugs; they also need effective remedial teaching! However, in the absence of treatment, teaching is less effective.

Ecological approaches - for example, to control the water vegetation on which the snails that carry schistosoma feed, especially in water that people enter to wash or bathe, can also obviously be of value. Basic hygiene measures, especially around the safe preparation of food and drink, are highly desirable and largely effective in preventing re-infection and education programmes rightly concentrate on these.

Schistosomiasis and HIV

Schistosomiasis (formerly bilharzia) is a debilitating disease caused by five species of parasitic worms or helminths in the genus Schistosoma, which are also known as blood flukes.

The adult worms are around 10mm long and live in peoples veins for 20 to 30 years, causing damage in either the lower bowel or the bladder (depending on the species). Eggs are shed into the bloodstream, many of which collect in the liver where they too cause damage over time. Eggs also pass into water where they rest on water plants until eaten by snails in which they grow into larvae that are then shed into the water. These larvae then enter the bodies of people who come into contact with the water.

Schistosomiasis is present in Africa, South East Asia, parts of Latin America and the Caribbean. It is particularly common in Africa, including Egypt, with two of the three main kinds S. mansoni (eggs shed into faeces) and S. haematobium (eggs shed into urine) being present. The third most important species, S. japonicum, is found in Asia and is similar to S. mansoni.

Around 200 million people are infected with schistosomes in 74 countries, of whom perhaps 20 million are severely ill and many more have some symptoms. The economic impact is reportedly second only to malaria in reducing productivity at work and in limiting childrens ability to learn.

Irrigated agriculture which creates permanent shallow freshwater channels has been a major factor promoting the spread of schistosomiasis. Control measures aim to reduce the numbers of water plants and snails, treat sewage and keep it out of irrigation water, and reduce exposure to water that is infested with the larvae.

The standard treatment for schistosomiasis is a drug called praziquantel (Cysticide), which is highly effective in a single dose (for S. haematobium) or two doses, four to six hours apart, on a single day (S. mansoni). It costs as little as $0.25 per treatment for adults and even less for children. Correct dosage varies with body weight as well as the species of worm. Praziquantel is the basis for mass treatment campaigns and has rendered a number of older treatments obsolete. Although treatment is not 100% effective, drug resistance has not yet been reported. Side effects are usually minor, though use in pregnancy should be avoided if possible. It kills several other varieties of worm, which is usually an advantage but is occasionally a hazard since dead worms can cause problems if present in the eye or the brain.

However, recent work has suggested that praziquantel may be less effective in HIV-positive patients, since it requires a strong immune system to kill the worms in the body^[1]. Further studies are required to establish whether the drug needs to be given at higher doses or more often in patients with HIV, in order not only to reduce the number of eggs released by the worms, but also to kill the worms themselves.

Alternative treatments which are still in use include oxamniquine, used to treat intestinal schistosomiasis, and metrifonate, used to treat urinary infections with S. haematobium.

A Kenyan study found that HIV-positive men with low CD4 cell counts, due to HIV, are at higher risk of re-infection with the worms that cause schistosomiasis than adults with undamaged immune systems. Taken with other evidence, including resistance to re-infection that appears with age and following drug treatment that kills the worms, the researchers argue that a preventive vaccine may be possible. However, more research is needed to understand the immune responses leading to resistance (Karanja).

The Kenyan team studied 96 male car-washers in Kisumu from 1995 to 1999 who were routinely exposed to the worms in the shallow waters of Lake Victoria where they stood while washing down vehicles. Careful records were kept of the number of cars each man had washed, as a basis for payment. These turned out to be a good measure of the level of risk of reinfection with schistosomiasis.

All men had blood taken for CD4 cell counts and stool and urine samples taken for schistosomiasis, which was treated as soon as eggs were found. Of around 100 men recruited into the study, 30% were HIV positive to begin with and the rate of new infections was above 8% per person per year. This allowed a comparison to be made of reinfection rates among groups of men with different CD4 counts, HIV-positive and HIV-negative. Once other factors were taken into account, they estimated that HIV-positive men with a CD4 count below 100 cells per mm³ had a 1.37 times higher re-infection rate than HIV-negative men.

An ongoing study from Zimbabwe, the Mupfure Schistosomiasis and HIV cohort, has failed to confirm previous reports by Karanja and others that people with HIV were less likely to shed schistosomes in their urine than people without HIV. It has also reported that CD4 cell count is unaffected by treatment of S. haematobium regardless of HIV status (Kallestrup 2003).

Schistosoma worms have a complex effect on the immune system of the people they infect, some of which may be the direct result of substances secreted by the worms. It has been proposed that these make people more susceptible to diseases such as HIV and tuberculosis.

Another potential interaction occurs when schistosomiasis occurs in the veins around the female genital tract (Feldmeier; Poggensee) and this might facilitate heterosexual HIV transmission in either direction. The same could also apply to male genital infection (Leutscher).

Blood loss from Schistosoma infections and other helminths, especially intestinal hookworms, is a common cause of anaemia. This may also contribute to anaemia among people with HIV, which leads to substantially raised mortality.

Other helminths and HIV

Researchers in Ethiopia (Wolday) have reported an association between the treatment of intestinal worms and a reduction in HIV viral load, in people coinfected with worms and HIV.

56 asymptomatic HIV positive adults who had not been diagnosed with AIDS-related diseases (26 men, 30 women) were recruited for this study, 31 of whom had intestinal worms at the time of enrolment, diagnosed from stool samples, while 25 did not. All 56 were treated (in case some infestations were missed) with 200mg of albendazole daily for three days on three occasions at baseline, 3 and 6 months. In addition, those who were diagnosed with schistosomiasis were treated with 40mg/kg of praziquantel. Eggs in stool samples were used as a measure of the level of worm infestation.

Most of the worms detected were Trichurus trichiura (14 cases) or Ascaris lumbricoides (13); schistosomiasis was rarer, with S. mansoni (4) and S. stronglyoides (2).

Viral load tests were done in Chicago, USA, on blinded plasma samples; CD4 counts were also measured, in Ethiopia, using a FACScount system.

At baseline, there was a weak, non-significant association between viral load and having worms or not; however, among those who did have worms, there was a highly significant correlation between the number of worm eggs in stools and viral load.

Some worm infestations were successfully treated and others were not, or people were reinfested by the same or a different kind of worm. In 28 people it was possible to compare viral loads before and 6 months after treatment, in three groups: 12 successfully treated, 6 unsuccessfully treated, 9 with no infestation. (6 people died or were lost to follow-up; for others, viral load results were not available at both time points.)

Viral load fell in the treated group, by -0.36 log copies/ml on average, but rose by 0.69 log in the persistent or re-infestation group and by 0.14 log in the apparently worm-free group (a difference of almost 1 log, equivalent to antiviral effect of dual combination therapy). The results achieved statistical significance (p=0.04) despite the small numbers involved. Since even the worm-free group had received anti-worm treatment, it was not a direct antiviral effect of the treatment. There was no significant change in CD4 cell count in any group between baseline and month 6, however.

The authors observe that some studies of schistosomiasis have not seen such effects; they suggest that Trichurus and Ascaris infestations have a shorter-lasting effect on the immune system, so that treatment more rapidly leads to a reduction in viral load.

In view of the very large numbers of people with HIV who are infested with intestinal worms and the low cost of treating them, even a modest effect could be of great public health value. However, larger studies are still needed to test the value of de-worming to prevent disease progression and HIV transmission, for example, from mothers to babies. In addition to a direct effect on viral load, treating intestinal worms improves peoples nutritional status, which is also likely to improve their ability to live with HIV.

Researchers working in Khayelitsha, in Western Cape Province, South Africa, where soil-transmitted helminths like Ascaris and Trichuris are hyperendemic, have also explored the interaction between these infections and HIV (Fincham). They found that raised levels of IgE antibodies (which are induced indiscriminately by some worms as a self-defence mechanism, to protect themselves against specific IgE antibodies) correlated with reduced CD4 counts in people with HIV. To give an idea of the scale of worm infection in such a setting, more than 90% of primary school children are infected, and 40% of an adult volunteer sample recruited for a study had worm eggs in their faeces.

References

Bentwich Z. Eradication of helminthic infections will have a major impact on pathogenesis of AIDS in developing countries and on success of protective HIV vaccines. Antiviral Therapy 8 (Suppl. 1): abstract 1013. 2003.

Feldmeier H et al. Female genital schistosomiasis as a risk factor for the transmission of HIV. International Journal of STD and AIDS 5: 368372, 1994.

Fincham JE et al. Interaction between co-endemic HIV/AIDS and worm infestation in adults living in Khayelitsha. South African AIDS Conference, Durban, poster T1-P40, 2003.

Kallestrup P et al. Schistosomiasis and HIV in co-infected individuals - egg excretion, XIV International Conference on AIDS, Barcelona, abstract WeOrC1376, 2002.

Kallestrup P et al. Schistosomiasis & HIV - effect of treatment with praziquantel on CD4 counts. Thirteenth ICASA, Nairobi, abstract 156877, 2003.

Karanja DMS et al. Resistance to reinfection with Schistosoma mansoni in occupationally exposed adults and effect of HIV-1 co-infection on susceptibility to schistosomiasis: a longitudinal study. The Lancet 360: 592-596, 2002.

Karanja DM et al. Studies on schistosomiasis in western Kenya. I. Evidence for immune-facilitated excretion of schistosome eggs from patients with Schistosoma mansoni and human immunodeficiency virus co-infection. American Journal of Tropical Medicine and Hygiene 56: 515521, 1997.

Karanja DM et al. Studies on schistosomiasis in western Kenya. II. Efficacy of praziquantel for treatment of schistosomiasis in persons coinfected with HIV-1. American Journal of Tropical Medicine and Hygiene 59: 307311, 1998.

Leutscher P et al. Genital schistosomiasis in males a community-based study from Madagascar. Lancet 355: 117118, 2000.

Poggensee G et al. Female genital schistosomiasis of the lower reproductive tract: prevalence and schistosome-related morbidity. Journal of Infectious Diseases 181: 12101213, 2000.

Poggensee G et al. Schistosomiasis of the female genital tract: public health aspects. Parasitology Today 15: 378381, 1999.

WHO Fact Sheet no 115, Schistosomiasis, May 1996.

Wolday D et al. Treatment of intestinal worms is associated with decreased HIV plasma viral load. JAIDS 31: 56-62, 2002.