Artemether, an effective new agent for chemoprophylaxis against shistosomiasis in China: its in vivo effect on the biochemical metabolism of the Asian schistosome.

Conventional drug chemotherapy against human schistosomiasis currently relies on treatment with praziquantel to eliminate adult schistosome worm pairs. The use of praziquantel for control purposes is limited, however, by high rates of post-treatment re-infection with subsequent parasite egg deposition and host end-organ damage. Artemether, a methyl ether derivative of the anti-malarial drug quinghaosu, was discovered recently to also have anti-schistosomal properties. Because artemether selectively targets the larval migratory stages of the parasite, known as schistosomulae, it blocks the development of ovipositing adult schistosome worm pairs in the vasculature. On this basis, we have since shown in clinical trials conducted in China that artemether has proven benefit as an agent for chemoprophylaxis. In vivo studies using laboratory animals suggest that artemether causes damage to the tegument and musculature of schistosomulae. Artemether may exert its helminthotoxic effect through synergy with hemin or related heme-containing compounds. Schistosomes recovered from artemether treated laboratory animals have increased glycogen phosphorylase activity, but decreased glucose uptake. These findings may account for their decreased glycogen content, relative to schistosomes recovered from untreated laboratory animals. The artemether-damaged schistosomes also have decreased activities of a number of enzymes and enzyme systems, including glycolysis. This might suggest common pathways by which artemether may target human parasites that live in the bloodstream.

Epidemiology of human ancylostomiasis among rural villagers in Nanlin County (Zhongzhou Village), Anhui Province, China: II. Seroepidemiological studies of the age relationships of serum antibody levels and infection status.

Anti-hookworm antibody serologic responses were measured in residents of an Anhui provincial Chinese village where Ancylostoma duodenale is the predominant hookworm. Antibody responses were measured against either soluble infective third-stage larval (L3) or adult antigens. Immunoglobulins of the IgG class, especially IgG4 correlated with both the prevalence and intensity of A. duodenale hookworm infections. In contrast, there was an inverse correlation with IgM, but no correlation with IgA or IgE. Circulating IgG4 antibody responses might serve as a surrogate marker for active A. duodenale hookworm infection.

Epidemiology of human ancylostomiasis among rural villagers in Nanlin County (Zhongzhou village), Anhui Province, China: age-associated prevalence, intensity and hookworm species identification.

Hookworm infection has traditionally been highly endemic to Anhui Province, China. Zhongzhou village in southwestern Anhui was identified as an endemic focus of infection caused by the hookworm Ancylostoma duodenale. This species was found to predominate over Necator americanus in ratios ranging from 35:1 based on the recovery of third-stage infective larvae (L,) to 21:1 based on the recovery of adult hookworms after anthelmintic chemotherapy. The overall prevalence of Ancylostoma infection in Zhongzhou was 33.2% with a greater prevalence among males. Unlike the age-associated prevalence patterns for N. americanus in Hainan and other southern Chinese provinces that show increasing prevalence with age and the highest prevalence among the elderly, the age-associated prevalence for A. duodenale in Zhongzhou exhibited a peak in middle-aged adults with subsequent decline. The age-associated intensity pattern exhibited a similar trend although the most of the hookworm infections were light or moderate infections as defined by quantitative egg counts.

Histochemical alterations of infective third-stage hookworm larvae (L3) in vaccinated mice.

To study the histochemical alterations of hookworm L3 administered in a challenge dose to mice vaccinated previously with the larvae. Male Kunming strain mice vaccinated subcutaneously with 500 living Ancylostoma caninum L3 once every 2 weeks for a total of three immunizations before a final challenge with 500 L3 one week after the final immunization. The abdominal skin with underlying subcutaneous tissue and muscle were removed from the site of percutaneous challenge entry (from 2-3 mice), and fixed in absolute alcohol, cold acetone and 10% neutralized formalin. The tissue sections containing the L3 from the challenge dose were then stained histochemically of glycogen, RNA, DNA alkaline protein, acid mucopolysaccharide, collagen, reticulin, alkaline phosphatase (AKP) and adenosine triphosphatase (ATPase). Skin samples from non-immunized mice that were also subcutaneously inoculated with the L3 served as negative control. The L3 identified in cutaneous sections from vaccinated mice at 6-72 hours post-challenge exhibited reductions in parasite glycogen, alkaline protein, RNA and DNA, as well as reductions in acid mucopolysaccharide, collagen and reticulin contents in the parasite cuticle. There were also reduced enzyme AKP and ATPase activities. In contrast L3, identified in sections from non-immunized mice exhibited a normal histochemical appearance, as did some L3 who survived in vaccinated mice at 7-14 days post-challenge. Vaccination results in hookworm L3 damage which is manifested by reduced histochemical staining for the challenge inoculum of parasites. There is also reduced hydrolytic enzyme activity. The observed changes could reflect either host-mediated parasite structural damage and disintegration or possibly anti-metabolic properties of the host immune response.

Epidemiology of human intestinal nematode infections in Wujiang and Pizhou counties, Jiangsu Province, China.

Intestinal nematode infections are considered highly endemic in the Chinese province of Jiangsu. In May 1997, the prevalence of intestinal nematodes infections was determined among all of the inhabitants aged 5 to 65 of the southern Jiangsu village of Yaojiakon (Wujiang County) and the northern Jiangsu village of Jianmiao (Pizhou County). It was determined that the prevalence of ascariasis, trichuriasis and hook worm infection was greatly reduced compared to when it was last measured in 1990. The reduction was noted to be particularly impressive in Yaojiakon village where the prevalence of ascariasis and trichiuriasis fell to 2% and 1.5% respectively. Much of this reduction was attributed to improvements in economic development which have occurred in southern Jiangsu Province at a rapid pace. In contrast, the reduction in nematode infections among villagers living in northern Jiangsu was more modest. The most striking reduction in both villages was in school-aged children who since 1988 have received yearly treatments with anthelminthic drugs. The intensity of nematode infections was investigated for hookworm where 70% of hookworm-infected Yaojiakon villagers were found to harbor light infections (< 400 eggs per gram) compared to 83% of hookworm-infected Jianmiao villagers. Necator americanus was the predominant hookworm in Yaojiakon village (South), whereas Ancylostoma duodenale predominated in Jianmiao village (North). The majority (76%) of hookworm-infected patients developed IgG antibodies against N. americanus antigen, although 20% of uninfected patients living in the village also had circulating antibodies. Intestinal nematode infections continue to be a significant public health problem in Jiangsu Province although their prevalence has decreased since 1990.