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Clinical picture, epidemiology and outcome of Loa-associated serious adverse events related to mass ivermectin treatment of onchocerciasis in Cameroon.

In August 2002, 65 cases of Loa-associated neurological Serious Adverse Events were reported after ivermectin treatment. The first signs, occurring within the 12-24 hours following treatment, included fatigue, generalized arthralgia, and sometimes agitation, mutism, and incontinence. Disorders of consciousness, including coma, generally appeared between 24 and 72 hours, and showed a rapid variation with time. The most frequent objective neurological signs were extrapyramidal. The patients presented with haemorrhages of the conjunctiva and of the retina. Biological examinations showed a massive Loa microfilaruria, the passage of Loa microfilariae into the cerebrospinal fluid, haematuria, and an increase in the C-reactive protein, all of which have been correlated with the high intensity of the initial Loa microfilaraemia. Eosinophil counts decreased dramatically within the first 24 hours, and then rose again rapidly. Electroencephalograms suggested the existence of a diffuse pathological process within the first weeks; the abnormalities disappearing after 3-6 months. Death may occur when patients are not properly managed, i.e. in the absence of good nursing. However, some patients who recovered showed sequelae such as aphasia, episodic amnesia, or extrapyramidal signs. The main risk factor for these encephalopathies is the intensity of the initial Loa microfilaraemia. The disorders of consciousness may occur when there are >50,000 Loa microfilariae per ml. The possible roles of co-factors, such as Loa strains, genetic predisposition of individuals, co-infestations with other parasites, or alcohol consumption, seem to be minor but they should be considered. The mechanisms of the post-ivermectin Loa-related encephalopathies should be investigated to improve the management of patients developing the condition.

Journal Article↗

[The efficacy and tolerance of ivermectin (Mectizan) prescribed for the patient with multiple filarial infections (Loa loa/Onchocerca and/or M. perstans)].

Administration of ivermectin (Mectizan) in Loa loa filariasis induces a significant decrease of microfilaria load within 3 to 15 days. The excellent tolerability of the drug in patients infested simultaneously by O. volvulus and Loa loa allows to use ivermectin in mass treatments in geographical areas where the same patients can be affected by several filariasis. There is almost no efficacy against Mansonella perstans. A second administration one month after the first one in Loa loa affected patients has not led to a complete disappearance of microfilaria; the tolerability has still been good. Efficacy on Ascaris lumbricoides appears to be excellent; further studies are necessary in the cases of trichuriasis, ancylostomiasis and strongyloidiasis.

Filariasis↗

A non-LTR retrotransposon from the Hawaiian Drosophila: the LOA element.

An interspersed sequence has been isolated from the genome of D. silvestris, a species endemic to the Hawaiian Islands. The LOA element is 7.7 kb long and its 3' end consists of (TAA)n tandem repeats. Five different LOA elements were isolated, of which three were truncated at their 5' ends. Large deletions within the elements were frequent. A consensus sequence of the LOA element has been constructed using the nucleotide sequence of three elements. Two overlapping open reading frames (ORF) are present in the LOA element. In ORF1 two 'cys' motifs characteristic for gag proteins are found. The protein translated from ORF2 has similarities with retroviral pol genes. A protein databank search revealed 22% to 25% identity with the reverse transcriptase domains of retrotransposons. This region also shows the pattern of invariant amino acid residues which are most conserved in retroviral reverse transcriptases. In ORF2 an integrase specific 'cys' motif and a conserved sequence of retroviral proteases were identified. Structural similarities with LINE-like elements suggest that the LOA element represents a new non-LTR retrotransposon.

Amino Acid Sequence↗

An example of measurement and reporting of periodontal loss of attachment (LOA) in epidemiological studies: smoking and periodontal tissue destruction.

The measurement and reporting of periodontal disease in epidemiological studies can be complex, with the common indices having well-recognised shortcomings. The aim of this study was to illustrate the use of the periodontal loss of attachment (LOA) approach in investigating the association between cigarette smoking and loss of periodontal attachment in a convenience sample of adults, in order to determine whether or not smoking was a risk indicator for periodontal disease. All participants were given a detailed periodontal clinical examination in two randomly assigned contralateral diagonal quadrants, with LOA measurements made at six sites per tooth. Information was also collected on participants' socio-demographic characteristics, oral hygiene practices, smoking history, and attitudes towards smoking. The 240 participants examined comprised 81 current smokers (CS), 79 former smokers (FS) and 80 nonsmokers (NS). Substantial differences and a gradient in disease existed for LOA among the three groups. CS exhibited the greatest (and NS the least) prevalence, extent, and severity of LOA. CS had more plaque and calculus than either of the other two groups, but the groups did not differ with respect to bleeding on probing. Overall, smoking was associated with the disease outcome, and this persisted after potential confounders were controlled using multivariate analysis. Although the observed differences may have been due to the self-selected nature of the sample, the gradient evident across the three smoking exposure groups suggests that smoking cessation can slow the progression of the disease. The LOA approach appears to be a versatile and informative method for recording, analysing, and presenting data on periodontitis in epidemiological studies.

Adult↗

Prevalence of L. loa and M. perstans filariasis in southern Cameroon.

The prevalence and microfilarial density of Loa loa and Mansonella perstans filariasis have been determined in three successive surveys in one village in the dense rainforest of Southern Cameroon. The prevalence of L. loa microfilaraemia was 30.9% with a geometric mean density of 81.4 microfilariae/30 microliter blood. There was no difference between men and women. The prevalence increased with age from 14.5% at 0-9 years to 52.9% at 40-49 years, whereafter it stablized. The microfilarial density increased until the age of 30-39 years. The highest densities have been found around noon, although the difference was not significant. The prevalence of M. perstans microfilaraemia was 26.6% with a median density of 2.0 microfilariae/30 microliter blood. Both prevalence and density were increasing with age and were higher for men than for women. The time of day that the blood sample was taken had no influence on the microfilarial density of M. perstans.

Adolescent↗

Biogeographic analysis of the Uhu and LOA elements in the Hawaiian Drosophila.

Two transposable elements have been isolated from the Hawaiian Drosophila, the Uhu and LOA elements. The Uhu element has been shown to be present in a group of closely related species, the planitibia subgroup of the picture-winged Drosophila. This study examines the distribution of the Uhu element in several other subgroups of the picture-winged Drosophila, as well as the modified-mouthparts and antopocerus groups of the Hawaiian Drosophila. The LOA element has a much more limited distribution, having only been found in representatives of the planitibia and grimshawi subgroups of the picture-winged Drosophila. For both the Uhu and LOA elements there is an inverse correlation between the copy number of the element and the age of the island on which the species is endemic, i.e., species endemic to the Island of Hawaii, the youngest island, have the highest copy number, while species endemic to Kauai, the oldest island, have the lowest copy number of the element. The correlation suggests there is a relationship between speciation and the activity of transposable elements.

Animals↗

Failed attempts at experimental transplantation and transmission of nocturnally-periodic simian Loa from monkey to man.

This paper describes unsuccessful attempts to induce a nocturnally-periodic infection with simian Loa in a human volunteer (the author of this paper) by means of 1. Transplanting adult simian Loa worms from a wild drill (Mandrillus leucophaeus) to man; and 2. Infecting the same volunteer by sub-cutaneous inoculation with infective larvae of simian Loa from a laboratory-bred, experimentally infected Chrysops silacea.

Journal Article↗

An integrated genetic, radiation hybrid, physical and transcription map of a region of distal mouse chromosome 12, including an imprinted locus and the 'Legs at odd angles' (Loa) mutation.

A variety of loci with interesting patterns of regulation such as imprinted expression, and critical functions such as involvement in tumour necrosis factor pathways, map to a distal portion of mouse chromosome 12. This region also contains disease related loci including the 'Legs at odd angles' mutation (Loa) that we are pursuing in a positional cloning project. To further define the region and prepare for comparative sequencing projects, we have produced genetic, radiation hybrid, physical and transcript maps of the region, with probes providing anchors between the maps. We show a summary of 95 markers and 91 genomic clones that has enabled us to identify 18 transcripts including new genes and candidates for Loa which will help in future studies of gene context and regulation.

Animals↗

[Serum immunofluorescence examination in loa ophthalmia (author's transl)].

Loaiasis is a chronic parasitic disease caused by the filaria Loa loa.As soon as the worm reaches the subconjunctival space local irration ensues. This so-called Loa ophthalmia necessitates immediate surgical intervention which can be performed under topical anesthesia, using the slit lamp. The indirect immunofluorescence technique represents a valuable diagnostic test,since it is usually difficult to demonstrate the microfilaria in the peripheral blood.

Adult↗

The Native Hawaiian Health Professions Scholarship program's impact on the community of Ko'olau Loa: a program report.

The Native Hawaiian Health Professions Scholarship was established as one component of the Native Hawaiian Health Care Act of 1988, which was later reauthorized as the Native Hawaiian Health Care Improvement Act of 1992. The Scholarship program was designed to develop Native Hawaiian primary health care professionals who would return to work in Native Hawaiian communities. To ensure this, scholarship recipients fulfill their scholarship agreement by working in medically unserved and underserved communities throughout Hawai'i. Since 1991, 121 scholarships have been awarded to Native Hawaiians training in different primary care professions including medicine, dentistry, nursing, midwifery, social work, and public health. Although the service obligation is attached to the scholarship as a means of "paying back," the intent is to provide an opportunity for graduates to establish a sense of social responsibility for the communities most in need. One of the communities benefiting from this program is Ko'olau Loa, a community that spans from Ka'a'awa to Pupukea on Windward O'ahu. Native Hawaiian Health Scholarship recipients, Kehau Santiago, Michele Shimizu, and Stephany Vaioleti live and continue to serve in the very community in which they fulfilled their service obligations. This article focuses on how the Native Hawaiian Health Scholarship Program--in particular, the three scholars--affected Ko'olau Loa.

Education, Professional↗

Effect of diethylcarbamazine on adult Loa in monkeys.

The effect of diethylcarbamazine citrate (DEC) treatment (43-150 mg kg-1 daily for 12-21 days) on adult Loa worms in five drills (Mandrillus leucophaeus) is described. In individual monkeys, between one-third and all of the adult worms survived the treatment, and most of the surviving females were still producing live microfilariae. These experiments provide direct evidence which may explain the common clinical experience that single courses of DEC do not always succeed in eliminating the signs and symptoms of loiasis in humans. Further work on the chemotherapy of loiasis in monkeys, using DEC and other filaricides, might improve the treatment of this disease.

Animals↗

[Hypotheses on the dynamic ecology of Loa infections].

In the light of the known data about epidemiological cycles of human and simian loiasis in Africa, and the eventual relationships between these infections, a hypothetical schema is presented, giving a whole view of the dynamic ecology of the Loa systems. This schema involves a primitive simian savannah cycle, from which, the filaria passing from monkey to man, a human savannah cycle, and then the classical human forest cycle are developed. The primitive savannah cycle could also be at the origin of simian forest cycles, but the exchanges between monkeys and man seem very unlikely inside the forest. Between the factors favouring the passage from one cycle to another,. the bush fires could have played are important role. Finally, the main factors of the geographical distribution of human loiasis are discussed.

Africa, Central↗

Recycled oceanic crust observed in 'ghost plagioclase' within the source of Mauna Loa lavas

The hypothesis that mantle plumes contain recycled oceanic crust is now widely accepted. Some specific source components of the Hawaiian plume have been inferred to represent recycled oceanic basalts, pelagic sediments or oceanic gabbros. Bulk lava compositions, however, retain the specific trace-element fingerprint of the original crustal component in only a highly attenuated form. Here we report the discovery of exotic, strontium-enriched melt inclusions in Mauna Loa olivines. Their complete trace-element patterns strongly resemble those of layered gabbros found in ophiolites, which are characterized by cumulus plagioclase with very high strontium abundances. The major-element compositions of these melts indicate that their composition cannot be the result of the assimilation of present-day oceanic crust through which the melts have travelled. Instead, the gabbro has been transformed into a (high-pressure) eclogite by subduction and recycling, and this eclogite has then been incorporated into the Hawaiian mantle plume. The trace-element signature of the original plagioclase is present only as a 'ghost' signature, which permits specific identification of the recycled rock type. The 'ghost plagioclase' trace-element signature demonstrates that the former gabbro can retain much of its original chemical identity through the convective cycle without completely mixing with other portions of the former oceanic crust.

Journal Article↗

Population structure in the endangered Mauna Loa silversword, Argyroxiphium kauense (Asteraceae), and its bearing on reintroduction.

Reintroduction of populations of endangered species is a challenging task, involving a number of environmental, demographic and genetic factors. Genetic parameters of interest include historical patterns of genetic structure and gene flow. Care must be taken during reintroduction to balance the contrasting risks of inbreeding and outbreeding depression. The Mauna Loa silversword, Argyroxiphium kauense, has experienced a severe decline in population size and distribution in the recent past. Currently, three populations with a total of fewer than 1000 individuals remain. We measured genetic variation within and among the remnant populations using seven microsatellite loci. We found significant genetic variation remaining within all populations, probably related to the recent nature of the population impact, the longevity of the plants, and their apparent self-incompatibility. We also found significant genetic differentiation among the populations, reinforcing previous observations of ecological and morphological differentiation. With respect to reintroduction, the results suggest that, in the absence of additional data to the contrary, inbreeding depression may not be a substantial risk as long as propagules for the founding of new populations are adequately sampled from within each source population before additional inbreeding takes place. The results further suggest that if mixing of propagules from different source populations is not required to increase within-population genetic variation in the reintroduced populations, it may best be avoided.

Asteraceae↗

[Discovery of Loa ophthalmia by the French ship's surgeon François Guyot (1742-1816)].

We are indebted to François Guyot (4. 10. 1742-13. 6. 1816) for the term "loa," designating a species of filaria, pathogenic in humans, which is common tropical West Africa. Biographical details about this French ship's surgeon are published here for the first time. On several slave-trading voyages between Africa and America, Guyot noticed that some of the negroes suffered from recurrent ophthalmia. He established that it was caused by a worm roaming around under the conjunctiva, and succeeded in extracting the parasite. In 26 May 1781 Guyot submitted a report on his findings to the "Académie Royale de Chirurgie" in Paris. This article discusses details of the report, which was hitherto believed lost.

Conjunctival Diseases↗

Solar radiation: absence of air pollution trends at Mauna Loa.

Measurements of solar radiation made at Mauna Loa, Hawaii, over a period of 13 years give no evidence that human activities affect atmospheric turbidity on a global scale. Short-term fluctuations in insolation appear to be associated with naturally produced tropospheric aerosols. The intrusion of volcanic dust into the stratosphere results in prolonged increases in atmospheric opacity due to the extended residence times of aerosols in the stratosphere.

Aerosols↗