Modelling onchocerciasis transmission and control

In 1990 the World Health Organization (WHO) coordinated Onchocerciasis Control Programme in West Africa (OCP) used this slogan for evaluating fifteen years of control of the parasitic disease onchocerciasis and for expressing its optimism about the future. Based on the obvious success of OCP and on the availability of a safe and effective drug (ivermectin), the UNDP/World BanklWHO Special Programme for Research & Training in Tropical Diseases (TDR) has announced onchocerciasis to be one of the tropical diseases with good prospects for worldwide elimination, at least as a public health problem (the others being Chagas disease, Lymphatic filariasis, and Leprosy!). To judge slogans and statements like these, and in particular to determine under which circumstances and with what strategies they could become a realistic perspective, one should perform an integrated and detailed study of the dynamics of the disease and the impact of control. Such a study should preferably be embedded in a comprehensive quantitative approach. In the light of this, the objectives of the work reported in this thesis were (1) to develop, quantify, and validate a model for the transmission and control of onchocerciasis in West African savanna and (2) to use this model for aiding decision making in the OCP. Through achieving these objectives we have tried to contribute to a better understanding of the dynamics of the parasite that causes the illness and the impact of intervention measures, and to the as yet successful combat against the disease. In the general introduction an outline will be given of the epidemiology and control of onchocerciasis. Secondly, an overview of the achievements of the OCP in controlling the disease in West Africa will be provided. Finally, a short history will be presented of the role of quantitative modelling within OCP prior to the work reported in this thesis

The reproductive lifespan of Onchocerca volvulus in West African savanna

Abstract The epidemiological model ONCHOSIM — a model and computer simulation program for the transmission and control of onchocerciasis — has been used to determine the range of plausible values for the reproductive lifespan of Onchocerca volvulus. Model predictions based on different lifespan quantifications were compared with the results of longitudinal skin-snip surveys undertaken in 4 reference villages during 13 to 14 years of successful vector control in the Onchocerciasis Control Programme in West Africa. Good fits between predicted and observed trends in skin microfilarial loads could be obtained for all villages. It is concluded that the reproductive lifespan of the savanna strain of O. volvulus lies between 9 and 11 years, and that 95% of the parasites reach the end of reproduction before the age of 13 to 14 years

Crystal structure, electronic, and magnetic properties of the bilayered rhodium oxide Sr3Rh2O7

The bilayered rhodium oxide Sr3Rh2O7 was synthesized by high-pressure and high-temperature heating techniques. The single-phase polycrystalline sample of Sr3Rh2O7 was characterized by measurements of magnetic susceptibility, electrical resistivity, specific heat, and thermopower. The structural characteristics were investigated by powder neutron diffraction study. The rhodium oxide Sr3Rh2O7 [Bbcb, a = 5.4744(8) A, b = 5.4716(9) A, c = 20.875(2) A] is isostructural to the metamagnetic metal Sr3Ru2O7, with five 4d electrons per Rh, which is electronically equivalent to the hypothetic bilayered ruthenium oxide, where one electron per Ru is doped into the Ru-327 unit. The present data show the rhodium oxide Sr3Rh2O7 to be metallic with enhanced paramagnetism, similar to Sr3Ru2O7. However, neither manifest contributions from spin fluctuations nor any traces of a metamagnetic transition were found within the studied range from 2 K to 390 K below 70 kOe.Comment: To be published in PR

Ivermectin, ‘Wonder drug’ from Japan: the human use perspective

Discovered in the late-1970s, the pioneering drug ivermectin, a dihydro derivative of avermectin—originating solely from a single microorganism isolated at the Kitasato Intitute, Tokyo, Japan from Japanese soil—has had an immeasurably beneficial impact in improving the lives and welfare of billions of people throughout the world. Originally introduced as a veterinary drug, it kills a wide range of internal and external parasites in commercial livestock and companion animals. It was quickly discovered to be ideal in combating two of the world’s most devastating and disfiguring diseases which have plagued the world’s poor throughout the tropics for centuries. It is now being used free-of-charge as the sole tool in campaigns to eliminate both diseases globally. It has also been used to successfully overcome several other human diseases and new uses for it are continually being found. This paper looks in depth at the events surrounding ivermectin’s passage from being a huge success in Animal Health into its widespread use in humans, a development which has led many to describe it as a “wonder” drug

The Immune Landscape of Cancer

We performed an extensive immunogenomic anal-ysis of more than 10,000 tumors comprising 33diverse cancer types by utilizing data compiled byTCGA. Across cancer types, we identified six im-mune subtypes\u2014wound healing, IFN-gdominant,inflammatory, lymphocyte depleted, immunologi-cally quiet, and TGF-bdominant\u2014characterized bydifferences in macrophage or lymphocyte signa-tures, Th1:Th2 cell ratio, extent of intratumoral het-erogeneity, aneuploidy, extent of neoantigen load,overall cell proliferation, expression of immunomod-ulatory genes, and prognosis. Specific drivermutations correlated with lower (CTNNB1,NRAS,orIDH1) or higher (BRAF,TP53,orCASP8) leukocytelevels across all cancers. Multiple control modalitiesof the intracellular and extracellular networks (tran-scription, microRNAs, copy number, and epigeneticprocesses) were involved in tumor-immune cell inter-actions, both across and within immune subtypes.Our immunogenomics pipeline to characterize theseheterogeneous tumors and the resulting data areintended to serve as a resource for future targetedstudies to further advance the field

Can ivermectin mass treatments eliminate onchocerciasis in Africa?

OBJECTIVE: To elucidate the conditions in which mass treatment with ivermectin reduces the transmission of Onchocerca volvulus sufficiently to eliminate infection from an African community. METHODS: ONCHOSIM, a microsimulation model for onchocerciasis transmission, was used to explore the implications of different treatment intervals, coverage levels and precontrol endemicities for the likelihood of elimination. FINDINGS: Simulations suggested that control strategies based exclusively on ivermectin mass treatments could eliminate onchocerciasis. The duration of treatment required to eliminate infection depended heavily on the treatment programme and precontrol endemicity. In areas with medium to high levels of infection, annual mass treatments with 65% coverage for at least 25 years were necessary. Model predictions suggested that durations exceeding 35 years would be required if there were much heterogeneity in exposure to vector bites and, consequently, wide individual variation in microfilaria counts. If the treatment interval were reduced from 12 to 6 months the time for completion of the programme could be more than halved and elimination could be accomplished in areas of hyperendemicity, provided that the effects of each treatment would be the same as with annual treatments. However, it was doubtful whether high coverage levels could be sustained long enough to achieve worldwide eradication. CONCLUSION: Elimination of onchocerciasis from most endemic foci in Africa appears to be possible. However, the requirements in terms of duration, coverage, and frequency of treatment may be prohibitive in highly endemic areas

Can ivermectin mass treatments eliminate onchocerciasis in Africa?

OBJECTIVE: To elucidate the conditions in which mass treatment with ivermectin reduces the transmission of Onchocerca volvulus sufficiently to eliminate infection from an African community. METHODS: ONCHOSIM, a microsimulation model for onchocerciasis transmission, was used to explore the implications of different treatment intervals, coverage levels and precontrol endemicities for the likelihood of elimination. FINDINGS: Simulations suggested that control strategies based exclusively on ivermectin mass treatments could eliminate onchocerciasis. The duration of treatment required to eliminate infection depended heavily on the treatment programme and precontrol endemicity. In areas with medium to high levels of infection, annual mass treatments with 65% coverage for at least 25 years were necessary. Model predictions suggested that durations exceeding 35 years would be required if there were much heterogeneity in exposure to vector bites and, consequently, wide individual variation in microfilaria counts. If the treatment interval were reduced from 12 to 6 months the time for completion of the programme could be more than halved and elimination could be accomplished in areas of hyperendemicity, provided that the effects of each treatment would be the same as with annual treatments. However, it was doubtful whether high coverage levels could be sustained long enough to achieve worldwide eradication. CONCLUSION: Elimination of onchocerciasis from most endemic foci in Africa appears to be possible. However, the requirements in terms of duration, coverage, and frequency of treatment may be prohibitive in highly endemic areas