John E. Fincham

Efficacy of albendazole against the whipworm Trichuris trichiura - a randomised, controlled trial

OBJECTIVES AND DESIGN To test the efficacy of albendazole against the whipworm Trichuris trichiura for school-based deworming in the south-western Cape, South Africa. Children infected with Trichuris were randomised to 3 doses of albendazole (400, 800 or 1200 mg), each repeated 4 times. The boy/girl ratio was 1. A group not infected with worms was treated with placebo, creating a negative control. SUBJECTS AND SETTING Pupils at a primary school serving a wine-producing area approximately 90 km east of Cape Town. OUTCOME MEASURES Trichuris cure rates and reduction in the number of eggs/g in faeces, as well as the infection dynamics of Trichuris and Ascaris during treatment with placebo. RESULTS Albendazole treatment was associated with Trichuris cure rates of 23% (400 mg), 56% (800 mg) and 67% (1200 mg) after the final treatment. The corresponding reductions in the number of eggs/g of faeces were 96.8%, 99.3% and 99.7%. Environmental pollution by human faeces was confirmed because worm egg-negative children in the placebo group became egg-positive while the study was in progress. CONCLUSION The 400 mg stat dose had a low Trichuris cure rate. To repeat the dose on 2 or 3 days would increase cost, reduce compliance and complicate management. Albendazole cannot be used in deworming programmes in South Africa because it is a Schedule 4 prescription medicine. De-scheduling is needed urgently, particularly because of high efficacy against hookworm in KwaZulu-Natal and neighbouring countries.

Recall of intestinal helminthiasis by HIV-infected South Africans and avoidance of possible misinterpretation of egg excretion in worm/HIV co-infection analyses

BackgroundAscariasis and HIV/AIDS are often co-endemic under conditions of poverty in South Africa; and discordant immune responses to the respective infections could theoretically be affecting the epidemic of HIV/AIDS in various ways. It is well-known that sensitisation to helminthic antigens can aggravate or ameliorate several non-helminthic diseases and impair immunisation against cholera, tetanus and tuberculosis. The human genotype can influence immune responses to Ascaris strongly. With these factors in mind, we have started to document the extent of long-term exposure to Ascaris and other helminths in a community where HIV/AIDS is highly prevalent. In more advanced studies, objectives are to analyse relevant immunological variables (e.g. cytokine activity and immunoglobulin levels). We postulate that when Ascaris is hyperendemic, analysis of possible consequences of co-infection by HIV cannot be based primarily on excretion vs non-excretion of eggs.MethodsRecall of worms seen in faeces was documented in relation to the age of adult volunteers who were either seropositive (n = 170) or seronegative (n = 65) for HIV. Reasons for HIV testing, deworming treatments used or not used, date and place of birth, and duration of residence in Cape Town, were recorded. Confidence intervals were calculated both for group percentages and the inter-group differences, and were used to make statistical comparisons.ResultsIn both groups, more than 70% of participants were aware of having passed worms, often both when a child and as an adult. Most of the descriptions fitted Ascaris. Evidence for significantly prolonged exposure to helminthic infection in HIV-positives was supported by more recall of deworming treatment in this group (p < 0.05). Over 90% of the participants had moved to the city from rural areas.ConclusionThere was a long-term history of ascariasis (and probably other helminthic infections) in both of the groups that were studied. In women in the same community, and in children living where housing and sanitation are better, Ascaris sero-prevalence exceeded egg-prevalence by two- and three-fold, respectively. For ongoing and future analyses of possible consequences of co-infection by Ascaris (and/or other helminths) and HIV/AIDS (and/or other bystander conditions), comparisons must be based mainly on disease-related immunological variables. Especially in adults, comparisons cannot be based only on the presence or absence of eggs in excreta.

Worms and Pediatric Human Immunodeficiency Virus Infection and Tuberculosis

To the Editor?Some useful data on human immunodeficiency virus (HIV) levels in African infants have been provided by Biggar et al. [1], and the virus load in HIV-infected children has been found by Kalish et al. [2] to be associated with the rate of disease progression. What is becoming increasingly obvious is that various factors influence the speed with which individuals in different parts of the world develop AIDS [1-4]. We wish to draw attention to an additional, and possibly highly relevant, factor in the whole conundrum. Exposure to helminthic antigens in utero has been found to generate cytokine responses similar to those observed in adults, and these immune reactions persist into childhood [5]. Whether this has implications for pediatric HIV infection and tuberculosis (TB) needs to be investigated. The reason is that the immunological type 2 response which predominates in helminthiasis is thought to adversely influence the course of HIV and Mycobacterium tuberculosis infection and to decrease the efficacy of vaccines [5-8]. Because the type 2 situation is characterized by eosinophilia, it is important to investigate whether the eosinophil itself [7, 8] has a direct role in determining virus levels [1, 2]. Progression to AIDS among African children, who frequently harbor large numbers of worms, is said to be more rapid than among their counterparts in Europe or the United States [9]; however, the timing of HIV transmission may account for some of the differences [4]. Likewise, a young child living in an area with a high prevalence of TB might, as a result of intrauterine exposure to helminthic antigens, be at greater risk of developing clinically evident TB than a child who has not been prenatally sensitized to worm antigens. Markers for a type 2 response in helminthiasis include an elevated IgE concentration and a high eosinophil count. Both are significantly reduced by successful treatment of helminthic infection, suggesting that a shift to a type 1 profile has taken place. The type 1 pattern is thought to provide better protection against progression of HIV and M. tuberculosis infection [6-8], and it certainly protects better against reactivation of TB [10]. To help elucidate the immunological mechanisms involved in resistance and susceptibility to pediatric HIV/AIDS and TB, studies using mass anthelmintic chemotherapy would be appropriate in areas where the prevalence of helminthiasis is high, particularly where vaccination strategies are being contemplated for controlling HIV in adults or controlling TB in adults or children [5].

Implications for neonatal HIV/AIDS and TB of sensitization in utero to helminths

Recent research 1xGood worms or bad worms: do worm infections affect the epidemiological patterns of other diseases?. Bentwich, Z. Reply. Parasitol. Today. 2000; 16: 312Abstract | Full Text | Full Text PDF | PubMedSee all References1 appears to support the concept that mass deworming might help to control the incidence and/or progression of HIV/AIDS and tuberculosis (TB) 1.xGood worms or bad worms: do worm infections affect the epidemiological patterns of other diseases?. Bentwich, Z. Reply. Parasitol. Today. 2000; 16: 312Abstract | Full Text | Full Text PDF | PubMedSee all References, 2.xCan eradication of helminthic infections change the face of AIDS and tuberculosis?. Bentwich, Z et al. Immunol. Today. 1999; 20: 485–487Abstract | Full Text | Full Text PDF | PubMed | Scopus (158)See all References, 3.xHIV/AIDS, helminths and eosinophilia. Fincham, J.E and Markus, M.B. HIV and AIDS: Current Trends. 1999; 5: 9–11See all References, 4.xCould non-selective anthelmintic treatment programmes contribute to control of the spread of HIV infection and AIDS?. Fincham, J.E et al. Trans. R. Soc. Trop. Med. Hyg. 1999; 93: 536PubMed | Scopus (6)See all References, 5.xGood worms or bad worms: do worm infections affect the epidemiological patterns of other diseases?. Bundy, D et al. Parasitol. Today. 2000; 16: 273–274Abstract | Full Text | Full Text PDF | PubMed | Scopus (59)See all References, 6.xMbeki and AIDS in Africa. Markus, M.B and Fincham, J.E. Science. 2000; 288: 2131Crossref | PubMedSee all References.Because the human foetus can become sensitized to helminthic antigen or antibody, resulting in persistence into childhood of this T-cell priming, we have extended the above hypothesis 7xWorms and pediatric human immunodeficiency virus infection and tuberculosis. Markus, M.B and Fincham, J.E. J. Infect. Dis. 2000; 181: 1873Crossref | PubMed | Scopus (9)See all References7. That is, in order for neonates perhaps to be better protected against HIV/AIDS, TB and possibly other infections, consideration needs to be given to steps that might minimize the chances of young women becoming infested by intestinal or other helminths. In fact, it is not known whether progression of non-helminthic disease in infants is affected by prenatal sensitization to worms. However, the immunological memory acquired to maternal helminthiasis during gestation appears to lead to diminished type 1 immunity induced by Bacillus Calmette-Guerin (BCG) vaccination of children 8xHelminth- and Bacillus Calmette-Guerin-induced immunity in children sensitized in utero to filariasis and schistosomiasis. Malhotra, I et al. J. Immunol. 1999; 162: 6843–6848PubMedSee all References8. Type 1 immunity is thought to be protective against HIV/AIDS and TB 1.xGood worms or bad worms: do worm infections affect the epidemiological patterns of other diseases?. Bentwich, Z. Reply. Parasitol. Today. 2000; 16: 312Abstract | Full Text | Full Text PDF | PubMedSee all References, 2.xCan eradication of helminthic infections change the face of AIDS and tuberculosis?. Bentwich, Z et al. Immunol. Today. 1999; 20: 485–487Abstract | Full Text | Full Text PDF | PubMed | Scopus (158)See all References, 3.xHIV/AIDS, helminths and eosinophilia. Fincham, J.E and Markus, M.B. HIV and AIDS: Current Trends. 1999; 5: 9–11See all References, 4.xCould non-selective anthelmintic treatment programmes contribute to control of the spread of HIV infection and AIDS?. Fincham, J.E et al. Trans. R. Soc. Trop. Med. Hyg. 1999; 93: 536PubMed | Scopus (6)See all References, 5.xGood worms or bad worms: do worm infections affect the epidemiological patterns of other diseases?. Bundy, D et al. Parasitol. Today. 2000; 16: 273–274Abstract | Full Text | Full Text PDF | PubMed | Scopus (59)See all References, 6.xMbeki and AIDS in Africa. Markus, M.B and Fincham, J.E. Science. 2000; 288: 2131Crossref | PubMedSee all References, 7.xWorms and pediatric human immunodeficiency virus infection and tuberculosis. Markus, M.B and Fincham, J.E. J. Infect. Dis. 2000; 181: 1873Crossref | PubMed | Scopus (9)See all References.Further studies, such as the clinical immunological investigations in which we are involved, should in time, contribute to clarification of the situation.

Atherosclerosis: Aortic Lipid Changes Induced by Diets Suggest Diffuse Disease With Focal Severity in Primates That Model Human Atheromas

Atherosclerosis in Vervet or African Green monkeys (Cercopithecus aethiops) models the morphology and cytology of the disease of humans, and it is well established that the rate of atherogenesis in Vervets is influenced by diet. Aortic intimal concentrations of lipids and phospholipids known to be major components of atheromas were determined in female Vervets fed for 4 years on either an atherogenic (AD) or a prudent Western diet (PD). Lipid concentrations detectable microscopically as cholesterol crystals and foam cells were confirmed biochemically. In addition, the AD was associated with diffuse, invisible accumulation of lipids throughout aortic tissue to the extent that tissue with no fatty streaks or plaque (AD) contained the same or more lipids than visible fatty streaks (PD). Correlations between lipid concentrations and atherosclerosis were highly positive, which supports known correlations between aortic, plasma, and dietary lipids during atherogenesis, and validates the aortic lipid analysis. These aortic lipid concentration results imply that atherosclerosis is not confined to focal pathologic anatomy, but in terms of lipid components of the disease, it develops throughout the arterial system of Old World omnivorous primates. If the results are applicable to people, they provide new insight and emphasize the need to minimize dietary sources of atherogenic lipids.

Squamous Cell Carcinoma in an African Green Monkey

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Helminths and atopy

Atopic allergic diseases are reaching epidemic proportions in both developed and developing countries 1xThe epidemic of allergy and asthma. Holgate, S.T. Nature (Suppl). 1999; 402: B2–B4Crossref | PubMedSee all References1. T-helper cell type 2 (Th2) immune responses are common to atopic disorders and helminthic infections, which are widespread in underdeveloped regions. In a useful review, Mao et al.2xThe link between helminthic infection and atopy. Mao, X.-Q et al. Parasitol. Today. 2000; 16: 186–188Abstract | Full Text | Full Text PDF | PubMed | Scopus (31)See all References2 state that no definitive conclusion can be drawn as to the relationship between atopy and helminthic infection. Another unanswered question is whether these conditions can predispose patients to AIDS and TB. An immune profile dominated by Th1 cytokines appears to be required for protection against AIDS and TB (Refs 2xThe link between helminthic infection and atopy. Mao, X.-Q et al. Parasitol. Today. 2000; 16: 186–188Abstract | Full Text | Full Text PDF | PubMed | Scopus (31)See all References, 3xCan eradication of helminthic infections change the face of AIDS and tuberculosis?. Bentwich, Z et al. Immunol. Today. 1999; 20: 485–487Abstract | Full Text | Full Text PDF | PubMed | Scopus (158)See all References, 4xHIV/AIDS, helminths and eosinophilia. Fincham, J.E and Markus, M.B. HIV and AIDS: Current Trends. 1999; 5: 9–11See all References, 5xCould non-selective anthelmintic treatment programmes contribute to control of the spread of HIV infection and AIDS?. Fincham, J.E et al. Trans. R. Soc. Trop. Med. Hyg. 1999; 93: 536PubMed | Scopus (6)See all References, 6xWorms and pediatric human immunodeficiency virus infection and tuberculosis. Markus, M.B and Fincham, J.E. J. Infect. Dis. 2000; 181: 1873Crossref | PubMed | Scopus (9)See all References).However, exposure to helminthic antigens in utero results in generation of cytokine responses similar to those found in adults. The ability of primed T cells to react accordingly can persist into childhood 7xHelminth- and Bacillus Calmette-Guerin-induced immunity in children sensitized in utero to filariasis and schistosomiasis. Malhotra, I et al. J. Immunol. 1999; 162: 6843–6848PubMedSee all References7. This represents a potential complicating factor that should be considered when researching the link between worm infestation and atopic disorder in areas where helminthiasis is endemic. Suggestions for work of this nature are provided by Mao et al.2xThe link between helminthic infection and atopy. Mao, X.-Q et al. Parasitol. Today. 2000; 16: 186–188Abstract | Full Text | Full Text PDF | PubMed | Scopus (31)See all References2