Edward S Cooper

Intestinal nematode infections in children : the pathophysiological price paid

The mechanism by which small animals such as rodents resist or eliminate nematode parasites requires mucosal inflammation as the final effector of the immune response. The resulting freedom from chronic infection may be worth the price of short-term illness. Putative vaccines which attempt to enhance the natural effect will have to take into account the inflammatory cost to the host. Human helminthiases involve a more stable equilibrium between host and parasite. The medical literature on hookworm disease and clinical ascariasis describes, for the former, some chronic inflammatory effects correlated with worm burden, but for the latter a less quantified or predictable set of detrimental effects. We describe a current, systematic study of the inflammatory response to whipworm infection, in which anaemia, growth retardation and intestinal leakiness are viewed as predictable consequences related to infection intensity. There is evidence for the absence of cell-mediated immunopathology. However, a specific, IgE-mediated local anaphylaxis may, at least partly, mediate the deleterious effects. Increased numbers of mucosal macrophages may also contribute to the chronic, systemic effects through their output of cytokines. Similar attempts to show the mechanisms of pathogenesis and quantify the effects of hookworm disease should be undertaken.

Population distribution of Trichuris trichiura in a community of Jamaican children

The Trichuris trichiura worm burdens of 23 children living in a Place-of-Safety in Kingston, Jamaica, were assessed by stool collection for more than five days after treatment with mebendazole. This procedure was repeated after a seven-month period of natural re-infection. For both collections the maximum rate of worm expulsion was achieved on the fourth day after starting treatment. The worm population distributions were overdispersed and well described by the negative binomial probability model (k = 0.29) in each case. For any one individual, the number of worms passed on the first expulsion was unrelated, absolutely or relatively, to the number passed on the second. These data suggest that: knowledge of the time dependency of helminth expulsion is essential for the accurate estimation of worm burdens by this method; populations of Trichuris are more highly aggregated than those of Ascaris and may thus be more susceptible to control by selective rather than random chemotherapy; and the inherent predisposition of hosts to infection may be of minor importance in determining the distribution of worms in the population-heavily infected hosts appear no more or less likely to acquire large worm burdens on subsequent exposures.

Frankincense and myrrh as remedies in children.

Two cases of therapy with frankincense and myrrh in children are presented. The long history of this unusual treatment is outlined, demonstrating that for several millenia such agents have been employed in a number of medical contexts, as well as in the perfume and incense industries. Myrrh has found recent pharmacological application in the reduction of cholesterol and triglycerides, as predicted by several traditional therapies.

Population dynamics and chemotherapeutic control of Trichuris trichiura infection of children in Jamaica and St. Lucia

Population dynamical parameters of Trichuris trichiura infections in children were estimated from longitudinal intensity and prevalence data from a population (n = 23) in a childrens home in Jamaica. The theoretical predictions of a deterministic model incorporating these parameters were approximated to observed horizontal-age prevalence data from a naturally infected population (n = 203) of children in a St. Lucian village, and a rough estimate of the basic reproductive rate (Ro = 8-10) of T. trichiura obtained. The findings suggest that T. trichiura populations are intrinsically more difficult to control by traditional mass-treatment chemotherapy (eradication requires greater than 91% of the population to be treated every 6 months for greater than 5 years) than are populations of Ascaris, but may be more susceptible to selective chemotherapy programmes which aim to treat only the most heavily infected individuals.

3. Mucosal macrophages and cytokine production in the colon of children with Trichuris trichiura dysentery

Mucosal macrophages and accessory cells have been studied by immunohistochemistry in the lamina propria of the colon of children with Trichuris trichiura dysentery syndrome (TDS). No difference was found in the numbers of cells recognized by the monoclonal antibodies CD11c, CD68, or RFD7 between TDS children and local controls. However, large numbers of cells were recognized by an antibody against calprotectin (an anti-bacterial glycoprotein found in tissue infiltrating-monocytes) in TDS colonic mucosa, but few in control colon. Large numbers of cells containing tumour necrosis factor alpha (TNF alpha) were also seen in TDS mucosa; cells isolated from TDS mucosa secreted more TNF alpha than cells from control mucosa; and children with TDS had high levels of circulating TNF alpha. Non-specific macrophage-mediated inflammation and local cytokine production may therefore play a role in the pathogenesis of TDS.

Rate of expulsion of Trichuris trichiura with multiple and single dose regimens of albendazole

The efficacy of multiple and single dose regimens of albendazole on Trichuris trichiura infection was evaluated by counting the number of worms expelled/day from two pair-matched groups of children, for nine days following therapy. The temporal patterns of worm expulsion were similar whether the children received a single 400 mg dose or two consecutive doses: no worms were passed before the second day, or after the sixth day, after intervention, and the maximum worm expulsion rate was attained on the fourth day. A second treatment six days after the first expelled no more worms. The results obtained here resemble those obtained previously with a three-day (600 mg) regimen of mebendazole in a study of heavily infected children. We conclude: that irrespective of dose, benzimidazole carbamates require the gut transit time plus 48 hours to immobilize T. trichiura; and that a single dose of albendazole is effective against light infections of T. trichiura but requires further evaluation with high intensity infections.

Histopathology and immunohistochemistry of the caecum in children with the Trichuris dysentery syndrome.

Caecal biopsy specimens from Jamaican children with the Trichuris dysentery syndrome (TDS) and age matched Jamaican controls were investigated by immunohistochemistry and by light microscopy. Biopsy specimens from all children (with TDS and controls) showed a mild to moderate increase in inflammatory cells. Except in the vicinity of the worm, where the epithelium was flattened, there was no other epithelial abnormality. Compared with controls, children with TDS had increased IgM lamina propria plasma cells and decreased intraepithelial T cells. There was also an increase in crypt epithelial cell proliferation. Lamina propria T cells (both activated and non-activated) were no more common in children with the Trichuris syndrome than controls. Epithelial cell HLA-DR and VLA-1 expression (which are increased in other colitides) were the same in both groups. Despite the presence of large worm burdens and chronic dysentery, therefore, only minor changes were seen in the caecal mucosa of children with TDS.

PERTUSSIS: HERD IMMUNITY AND VACCINATION COVERAGE IN ST LUCIA

In a single complete epidemic in St Lucia, an island too small to support constant clinical pertussis, the pertussis case rates in small communities (villages and small towns) with differing levels of vaccination coverage of young children were compared. The association between greater vaccination coverage and greater herd immunity was clear, despite the imperfect protection given to individuals. An analysis in terms of population dynamics is evidence against the theory that endemic subclinical pertussis maintains transmission in a highly vaccinated population. We suggest that with a homogeneous vaccination coverage of 80% of 2-year-old children pertussis might be eradicated from the island, and that this is a practicable experiment.

Neural tube defects in Jamaica following Hurricane Gilbert.

An increased incidence of obvious live-birth neural tube defects (i.e., spina bifida cystica and encephalocele) occurred in Jamaica 11 to 18 months after Hurricane Gilbert. The conceptions of the affected babies coincided with a rise in megaloblastic change in sickle cell patients, suggesting a wide-spread drop in dietary folate intake. A detailed history was taken from each of the 17 affected mothers (case subjects) and 51 unaffected mothers (matched control subjects). The case subjects reported a significantly lower mean intake of dietary folate in the periconceptional period (154 micrograms/day) than did the control subjects (254 micrograms/day). The temporary increase in neural tube defects was associated with a diet comparatively low in folate in the periconceptional period, suggesting the dietary level of folate that fails to protect against neural tube defects under natural conditions.

Treatment effects in Trichuris dysentery syndrome

Heavy infection with the geohelminth Trichuris trichiura causes the Trichuris dysentery syndrome (TDS). Growth retardation and anaemia are characteristic of TDS and both are associated with poor development. We have examined the growth and developmental responses to treatment in 19 children aged 27–84 months with TDS. Developmental levels (DQ) were measured with the Griffiths mental development scales. Compared with a control group matched for age, gender and neighbourhood, the TDS children initially had serious deficits in DQ (24 points, p < 0.001). After a year of anthelmintic treatment, the TDS children showed improvement in locomotor development (p < 0.001) compared with the controls. The TDS children also had initial deficits in height‐for‐age, weight‐for‐height, mid‐upper arm circumference and haemoglobin levels. They caught up rapidly in indices of wasting (weight‐for‐height and mid‐upper arm circumference) and showed steady improvement in height‐for‐age and haemoglobin levels. Catch‐up in height was comparable to that of children recovering from coeliac disease. The importance of continuing prevention after initial treatment is highlighted.