Precalcaneal congenital fibrolipomatous hamartoma: report of 2 cases.

Precalcaneal congenital fibrolipomatous hamartoma is a benign condition of infancy that is possibly underdiagnosed because of the lack of reports in the literature. Lesions become evident after the first months of life and may be troublesome to parents and physicians. Patients are frequently referred to the pediatric surgeon for evaluation. We report and discuss 2 typical cases.

Estimating a mosquito repellent's potential to reduce malaria in communities.

BACKGROUND & OBJECTIVES: Probability models for assessing a mosquito repellent's potential to reduce malaria transmission are not readily available to public health researchers. To provide a means for estimating the epidemiological efficacy of mosquito repellents in communities, we developed a simple mathematical model. STUDY DESIGN: A static probability model is presented to simulate malaria infection in a community during a single transmission season. The model includes five parameters- sporozoite rate, human infection rate, biting pressure, repellent efficacy, and product-acceptance rate. INTERVENTIONS: The model assumes that a certain percentage of the population uses a personal mosquito repellent over the course of a seven-month transmission season and that this repellent maintains a constant rate of protective efficacy against the bites of malaria vectors. MAIN OUTCOME MEASURES: This model measures the probability of evading infection in circumstances where vector biting pressure, repellent efficacy, and product acceptance may vary. [corrected] RESULTS & CONCLUSION: Absolute protection using mosquito repellents alone requires high rates of repellent efficacy and product acceptance. [corrected] Using performance data from a highly effective repellent, the model estimates an 88.9% reduction of infections over a seven- month transmission season. A corresponding reduction in the incidence of super-infection in community members not completely evading infection can also be presumed. Thus, the model shows that mass distribution of a repellent with >98% efficacy and >98% product acceptance would suppress new malaria infections to levels lower than those achieved with insecticide treated nets (ITNs). A combination of both interventions could create synergies that result in reductions of disease burden significantly greater than with the use of ITNs alone.

Mastocytosis in children: clinicopathological study based on 35 cases.

Immunohistochemical staining is useful in the diagnosis of bone marrow infiltration in systemic mastocytosis. However, it is not clear if antibody staining may be helpful in the diagnosis of cutaneous mastocytosis (CM). We studied the histological appearance of CM in 35 pediatric patients. Cases were assigned to three basic clinical groups: I--Urticaria pigmentosa (UP, n=29); II--Mastocytomas (n=4); and III--Diffuse Cutaneous Mastocytosis (DCM, n=2). The analysis of clinical information revealed an association between the presence of diarrhea and a higher number of cells/field. Nine doubtful cases, all of them macules, were selected based on the scarcity of mast cells (MC) and the absence or rarity of other inflammatory cells. We compared the number of cells identified in Giemsa and immunohistochemical stains in definite and doubtful cases. The intraclass correlation statistic tested the concordance between each staining method. All 9 dubious cases according to the Giemsa stain had their CM diagnosis confirmed by the immunohistochemistry analysis. The intraclass correlation between Giemsa and c-kit was good (0.7) when the number of MC was high. However, there was no correlation between the mast cells counts in the two different stains in the dubious cases. The immunohistochemistry with c-kit might make CM diagnosis easier, especially in the macular cases, when there is a lower number of MC.

The local immune response in ulcerative lesions of Buruli disease.

Buruli disease (BU) is a progressive necrotic and ulcerative disease of the skin and subcutaneous tissue caused by Mycobacterium ulcerans. BU is considered the third most common mycobacterial disease after tuberculosis and leprosy. Three clinical stages of the cutaneous lesions have been described in BU: pre-ulcerative, ulcerative and healed lesions. In this study we used immunohistochemistry and automated morphometry to determine the percentage of macrophages and of CD4/CD8 lymphocytes and their expression of interferon (IFN)-gamma, interleukin (IL)-10, tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta. Expression of these cytokines was correlated with the inflammatory response evaluated by histopathology. All the studied BU ulcerative cases showed extensive necrosis and chronic inflammation. The most important feature was the presence or absence of granulomas co-existing with a mixed pro-inflammatory/anti-inflammatory cytokine balance. When granulomas were present significantly higher expression of IFN-gamma was seen, whereas in ulcerative lesions without granulomas there was increased expression of IL-10 and significantly higher bacillary counts. These features correlated with the chronicity of the lesions; longer-lasting lesions showed granulomas. Thus, granulomas were absent from relatively early ulcerative lesions, which contained more bacilli and little IFN-gamma, suggesting that at this stage of the disease strong suppression of the protective cellular immune response facilitates proliferation of bacilli.

Cutaneous mastocytosis in children: a clinical analysis of 71 cases.

OBJECTIVE: To characterize the clinical features, response to therapy, evolution and prognosis of cutaneous mastocytosis in children. BACKGROUND: Mastocytosis in children, instead of being induced by a potentially oncogenic c-kit mutation, is probably a clonal disease with benign prognosis. METHODS: The clinicopathological features, evolution and response to treatment were analysed in 71 children with mastocytosis. RESULTS: There were 53 (75%) cases of urticaria pigmentosa, 12 (17%) cases of mastocytoma, and six (8%) cases of diffuse cutaneous mastocytosis. In 92% of cases disease onset was in the first year of life. There was a male predominance 1.8 : 1. Treatment did not modify the disease evolution. Eighty per cent of patients improved or had spontaneous resolution of the disease. CONCLUSION: The most frequent clinical form of mastocytosis was urticaria pigmentosa followed by mastocytoma and diffuse cutaneous mastocytosis. Darier's sign was present in 94% of cases. A negative Darier's sign does not rule out mastocytosis. In contrast to adults, mastocytosis in children usually has a benign course making sophisticated or invasive diagnostic tests unnecessary. A classification of paediatric cutaneous mastocytosis is proposed.

Expression of cyclooxygenase type 2 in lepromatous and tuberculoid leprosy lesions.

BACKGROUND: Leprosy is an infectious disease with two polar forms, tuberculoid leprosy (TL) and lepromatous leprosy (LL), which are dominated by T-helper (Th) 1 and Th2 cells, respectively. High concentrations of prostaglandin E2 produced by the inducible enzyme cyclooxygenase type 2 (COX-2) in LL could inhibit Th1 cytokine production, contributing to T-cell anergy. OBJECTIVES: To compare the COX-2 expression in LL and TL. METHODS: Skin biopsies from 40 leprosy patients (LL, n = 20; TL, n = 20) were used to determine by immunohistochemistry and automated morphometry the percentage of COX-2 immunostained cells. RESULTS: Most COX-2-positive cells were macrophages; their percentages in the inflammatory infiltrate located in the papillary dermis, reticular dermis and periadnexally were significantly higher in LL than TL (P < 0.001 by Student's t-test). CONCLUSIONS: The high expression of COX-2 in LL may be related to high prostaglandin production contributing to T-cell anergy.

Mating strategies and spermiogenesis in ixodid ticks.

Mate-seeking and sperm-transfer in the ixodid hard ticks, which include important vectors of zoonotic pathogens, generally reflect their peculiarly prolonged pattern of feeding. The metastriate ticks, including Dermacentor, Amblyomma, and Rhipicephalus, invariably attain sexual maturity and mate solely on their hosts. The more primitive prostriate Ixodes ticks, however, may copulate both in the absence of hosts and while the female engorges. These expanded opportunities for insemination complicate the mating systems of the Ixodes ricinus complex of species. In these ticks, autogenous spermatogenesis must precede host contact, whereas anautogenous oogenesis requires that the females store sperm. All hard tick males undergo a courting ritual before they can deposit their spermatophores within the female's genital tract. These diverse and prolonged patterns of sexual interaction provide opportunities for interactions between populations and individuals that may be relevant to the role of ticks as vectors of zoonotic pathogens.

Issues in public health entomology.

Public health entomology focuses on the population biology of vector-borne infections, seeking to understand how such pathogens perpetuate over time and attempting to devise methods for reducing the burden that they impose on human health. As public health entomology passes its centennial, a series of pervasive research themes and spirited debates characterize the discipline, many reflecting a tension between field and laboratory research. In particular, institutional support for population-based research and training programs has fallen behind that for those using modern lab-based approaches. Discussion of modes of intervention against vector-borne infections (such as deployment of genetically modified vectors, the role of DDT in malaria control, host-targeted acaricides for Lyme disease risk reduction, and truck-mounted aerosol spraying against West Nile virus transmission) illustrates the discipline's need for strengthening population-based research programs. Even with the advent of molecular methods for describing population structure, the basis for anophelism without malaria (or its eastern North American counterpart, ixodism without borreliosis) remains elusive. Such methods have not yet been extensively used to examine the phylogeography and geographical origins of zoonoses such as Lyme disease. Basic ecological questions remain poorly explored: What regulates vector populations? How may mixtures of pathogens be maintained by a single vector? What factors might limit the invasion of Asian mosquitoes into North American sites? Putative effects of "global warming" remain speculative given our relative inability to answer such questions. Finally, policy and administrative issues such as the "no-nits" dictum in American schools, the Roll Back Malaria program, and legal liability for risk due to vector-borne infections serve to demonstrate further the nature of the crossroads that the discipline of public health entomology faces at the start of the 21st Century.

Overdiagnosis and consequent mismanagement of head louse infestations in North America.

BACKGROUND: Lay personnel and many health care workers in the United States believe that head louse infestations caused by Pediculus capitis are exceedingly transmissible and that infested children readily infest others. Schoolchildren therefore frequently become ostracized and remain so until no signs of their presumed infestations are evident. Repeated applications of pediculicidal product and chronic school absenteeism frequently result. METHODS: To determine how frequently louse-related exclusions from schools and applications of pediculicidal therapeutic regimens might be inappropriate, we invited health care providers as well as nonspecialized personnel to submit specimens to us that were associated with a diagnosis of pediculiasis. Each submission was then characterized microscopically. RESULTS: Health care professionals as well as nonspecialists frequently overdiagnose pediculiasis capitis and generally fail to distinguish active from extinct infestations. Noninfested children thereby become quarantined at least as often as infested children. Traditional anti-louse formulations are overapplied as frequently as are "alternative" formulations. Pediculicidal treatments are more frequently applied to non-infested children than to children who bear active infestations. CONCLUSIONS: Pediculicidal treatments should be applied solely after living nymphal or adult lice or apparently viable eggs have been observed. Because health care providers as well as lay personnel generally misdiagnose pediculiasis, and because few symptoms and no direct infectious processes are known to result, we suggest that the practice of excluding presumably infested children from school may be more burdensome than the infestations themselves.

Density-dependent preprandial mating by deer ticks.

To determine whether the prevalence of preprandial insemination in deer ticks reflects their local abundance, we sampled adult ticks by flagging vegetation at selected sites in eastern Massachusetts in a standardized manner. Resulting female ticks were dissected to determine whether they contained endospermatophores, and the frequency of insemination was compared to the number of questing ticks flagged at each site. The prevalence of insemination correlated closely with density of ticks. The frequency of insemination increased linearly during the Ist 2 months during the fall. The mean daily probability of insemination during this period was about 1% when, on average, about 4 ticks were flagged per minute. A predictive equation was derived via multiple regression expressing deer tick abundance as a function of collection date and insemination prevalence (P < 0.05). The frequency of preprandial mating, thereby, was correlated with the abundance of questing deer ticks. Insemination prevalence increased predictably as the season of adult activity progressed. We conclude that a season-specific analysis of the frequency of preprandial insemination provides a robust indicator of the abundance of deer ticks that is unaffected by short-term fluctuations in the weather.

Spatially explicit model of transposon-based genetic drive mechanisms for displacing fluctuating populations of anopheline vector mosquitoes.

To evaluate the prospect of transposon-based genetic drive mechanisms for replacing African vectors of malaria with nonvector anopheline mosquitoes, we developed a spatially explicit simulation model that determined the likelihood that released transgenic mosquitoes may proceed to fixation or extinction under diverse conditions. We compared the effect on fixation of long breeding seasons with relatively subtle population fluctuations to short breeding seasons with severe bottlenecks. Assuming 100% transposition efficiency among heterozygotes with fitness varying between 50 and 100% of that of wild-type mosquitoes, we simulated releases of 1, 10, 50, 90, and 99% of transposon-bearers in relation to wild mosquitoes as well as 1 and 10% releases that were repeated annually. We also evaluated diverse patterns of release including linear, marginal, focused, and scattered distribution. Random dispersal provided the most rapid fixation of transposons within populations. More massive releases allowed longer persistence of transposon-bearers but did not promote fixation, especially when breeding seasons were long. Relative fitness of transposon-bearers, however, proved more powerful than pattern or number of releases in determining whether a construct will become fixed or extinct. Even when fitness approaches that of the wild-type, fixation of a construct may require 150 generations or more.

Virulence of vector-borne pathogens. A stochastic automata model of perpetuation.

To determine how virulence may be perpetuated in populations of vector-borne pathogens, we simulated their fitness in a stochastic simulation based on cellular automata. Thereby, directly transmissible pathogens that differed in virulence were permitted to compete for hosts with similarly virulent pathogens that could infect hosts remotely because they were vector-borne. Fitness was defined as the proportion of the host population infected with each pathogen at equilibrium. Virulent, directly transmitted pathogens prevailed solely when their infectivity was transient. When duration of infectivity exceeded that of host survival, the less virulent pathogen invariably prevailed. Although remotely transmitted virulent pathogens persisted somewhat longer than did virulent pathogens that were transmitted directly, they never perpetuated themselves. We conclude that populations of vector-borne pathogens may retain pathogenicity somewhat longer than do those that are directly transmitted, but that both kinds of pathogens tend to become nonvirulent.

Large scale production of the vertebrate infective stage (L3) of Onchocerca volvulus (Filarioidea: Onchocercidae).

Laboratory-derived Simulium yahense and S. sanctipauli females were used to produce large numbers of Onchocerca volvulus infective stage larvae (L3) for use in assessing the possible chemoprophylactic potential of ivermectin in the chimpanzee model. Engorgement rates and subsequent post-prandial survival were correlated with the time at which adult flies were offered a carbohydrate source following emergence and the age of flies that fed on microfiladermic volunteers.

The effects of ivermectin on transmission of Onchocerca volvulus.

Ivermectin, given to onchocerciasis patients as a single oral dose of 200 micrograms per kilogram of body weight, substantially reduced the uptake of Onchocerca volvulus microfilariae by Simulium yahense, an efficient black fly vector of the parasite in the tropical rain forests of West Africa. Three months after treatment, patients given ivermectin infected flies at a significantly lower rate than those who had received diethylcarbamazine or placebo, thereby reducing the number of developing larvae in the vector population. This diminished rate of infectiousness was also evident 6 months after treatment. These results strongly suggest that ivermectin could be effective in interrupting transmission of Onchocerca volvulus for epidemiologically important periods of time.