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Pharmacological antagonist interventions
C H A P T E R
5 Pharmacological antagonist interventions J.J. Walsh Emeritus Distinguished University Professor of Marine Science, University of South Florida, United States
I once read a silly fairy tale, called “The Three Princes of Serendip”: as their Highnesses travelled, they were always making discoveries, by accidents and sagacity, of things which they were not in quest of. Walpole (1754) Similar to the parallel uses of Ephedra spp. in Peru and China, as well as black henbane Hyoscyamus niger (Alizadeh et al., 2014) described in this book earlier within sections on Egypt and Yucatan, Mexico, the pragmatic “whatever worked” approach of these bronchodilators was employed after trial, error, and success histories of multiple afflicted human societies. Before development of synthetic anticholinergic agents in the 1990s, atropine was a natural alkaloid then obtained globally from H. niger after B1833. By 1901, it was first available in asthma cigarettes, as described by Marcel Proust that year in a letter to his mother: Yesterday after I wrote to you I had an attack of asthma and incessant running of the nose, which obliged me to walk all doubled up and light anti-asthma cigarettes at every tobacconist’s I passed (Jackson, 2010). However, like other members of the deadly nightshade Atropa belladonna plant family, H. niger, as well as mandrake Mandragora officinarum and Jimson weed Datura spp., all also contained other alkaloid poisons hyoscine, hyoscyamine, and scopolamine—in addition to atropine. About 3040 seeds of these plants were fatal. Recall that drops of henbone, dripped in his ear, were used to kill the king of Denmark, while he slept in Shakespeare’s play Hamlet. Later other examples of serendipity were the development and uses of penicillin, chloral hydrate, lithium (Ban, 2006), and quinine. The Amazon jungle harbored over 80,000 species of higher plants by 1970, with unknown medical benefits (Schultes, 1969, 1988, 1994, 1999; Prance, 1970, 1972; Schultes and von Reis, 1995; Lawn et al., 2017). But some of those less benign terrestrial drugs and foods there were instead rejected and/or
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used as curare arrow toxins (Table 1.1) by local Amerindians as malign nonstrychnine poisons—but it is the dose alone that makes a poison [Paracelsus (P. von Hohenheim), 1540; Bisset, 1995], like those also discussed here—after blown ashore from the seas.
5.1 Serendipity of penicillin emergence Prior human lung penetrations of parasitic fungi had resulted in subsequent diversions of human biochemical syntheses to form more Th2 cytokines of our immune system (Lucey et al., 1996) to instead deal with allergens rather than Th1 to squelch internal parasite poisons, with at times deadly consequences. Yet, among the 65,000 species of filamentous ascomycete fungal species, some were not benign, such as Penicillium spp. sources of antibiotics. After the serendipitous discovery in 1928 by Alexander Fleming in St. Mary’s Hospital, London, of the antibacterial toxicity of airborne laboratory Penicillium notatum against Staphylococcus (Fleming, 1929), the progress toward Paul Ehrlich’s alternative magic bullet chemotherapy, e.g., use of methylene blue dye (Oz et al., 2011) against malarial protozoan hosts (Guttmann and Ehrlich, 1891), then also accelerated (Lu et al., 2018) as an alternative to quinine therapy. Since the yields of penicillin from P. notatum’s biochemical syntheses were small, however, in 1943 at the Northern Regional Research Laboratory of the Bureau of Agricultural and Industrial Chemistry at Peoria, Illinois, additional fungal sources of penicillin were sought from the surrounding fertile cultivated soils, decomposing fruits and vegetables, and moldy food products of bread, cheese, and cured meats. Another 10-fold greater penicillin producer, Penicillium chrysogenum, compared to P. notatum, was then isolated there from .25 strains of that former group (Raper et al., 1944). Yet in addition to bacteriacaused infectious diseases of pneumonia and tuberculosis, which penicillin and other antibacterials alleviated, unfortunately parasitic protozoans continued to also yield fatal human cases of malaria and sleeping sickness.
5.2 Quinine remedies for other infectious diseases The local Andean drug uses of ephedrine and theophylline to deal with exacerbating allergenic pulmonary maladies and quinine to treat jointly concurrent malaria infections probably began by at least 4500 BCE, when legends say that the Inca Viracocha came out of the Pacific Ocean to found his capital city in the Cuzco Valley. Indeed, other serendipitous discoveries of beneficial pulmonary drugs were also global processes, first documented by the Han Chinese herbalist Shen Nung in his description of the use of Mongolian Ephedra sinica during 2800 BCE in his Pen Ts’ao Kang-mu (Compendium of Materia Medica), written in 1578. Further Ephedra vignettes were recorded: in 60,000-year-old burial sites of Iran; more comments by Pliny of Rome during the first century CE; and then expanded scientific and public audiences over the last few decades (Chevallier, 1996; Fillon, 2003; Schultes and von Reis, 1995). After their 16th-century arrival in the New World, Spanish Jesuit missionaries learned from indigenous Incas of Peru about a medicinal bark, used for the treatment of malarial fevers. With this bark, the Countess of Chincho´n, the wife of the Viceroy of Peru, was supposedly cured in Lima during 1638 of her fever. In any event, the bark from the tree was
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then called Peruvian bark, and the tree was named Cinchona officinalis after the Countess. The medicine from the bark was then known as the antimalarial alkaloid quinine. Along with artemisinins, quinine is still one of the most effective antimalarial drugs available today, despite early signs of quinine resistances of Plasmodium strains by 1907 in Brazil (Da Silva and Benchimol, 2014). In prior pre-Columbian use of quinine by Amerindians in South America, their pest targets may have been the parasites Plasmodium vivax in Venezuela within intermediate mosquito Anopheles darlingi hosts (Gabaldon, 1949), after presumed transits across North and Mesoamerica in other penultimate human hosts. As recently as 1970 on a southcentral Texas ranch, P. vivax infections of children were transmitted by another concurrent mosquito vector Anopheles pseudopunctipennis (Bruce-Chwatt, 1972). By 2010, P. vivax was still .85% of all malarial cases in Venezuela (Grillet et al., 2014) and Mexico (Gonzalez-Ceron et al., 2013). Near the southern border of Mexico with Guatemala in the Mexican State of Chiapas during 201014, larvae of A. darlingi also still occurred in mainly freshwater forest habitats (Villarreal-Trevino et al., 2015). The genome of this species of malarial protozoan parasites was evidently of simian origins in Southeast Asia about 46,00082,000 years ago (Escalante et al., 2005; Cornejo and Escalante, 2006). These microbial data supported the human genetic evidence (Hoffecker et al., 2014) for their anthropogenic transfers of the bacterial TB parasitic counterparts as well, from Northeast Asia to North, Meso-, and South America, albeit over just 14,00050,000 years ago, once Beringia appeared with an implied age of 32,000 years (Guidon and Delibrias, 1986). Other hypotheses recently suggested, however, that similar parasites to P. vivax may have also been hosted by African chimpanzees Pan troglodytes (Liu et al., 2014). Indeed, farther south in Brazil, Plasmodium falciparum of African gene pool origins (Yalcindag et al., 2012) from original primate Gorilla gorilla hosts (Duval et al., 2010), as well as those of chimpanzees, may have instead directly invaded South America multiple times within unwilling human hosts on slave ships during 15011888. Then, B4.9 million African slaves were landed at mainly the coastal cities of Rio de Janeiro and Salazar. Skeletal remains of those Brazilian slaves, with mean herbivore signatures of a del 15N (Bastos et al., 2016) of 18.8 o/oo (Table 1.5), also reflected that of other African slaves before transshipments from South Africa (Cox and Sealy, 1997). Yet, in the Brazilian Amazonas State, the percentage of the total malaria cases in 2009 due to P. falciparum was still only 15.3% (Oliviera-Ferreira et al., 2010), so that the relatively recent African protozoan immigrants had not yet replaced their older Asian competitors for that specific human parasite niche (Rodrigues et al., 2018). At the same time, the extant bone collagen of free Amerindians during B4001300 CE at the mouth of the Amazon River on Marajo Island, near Belem, was instead a mean del 15N of 111.2 o/ oo (Table 1.5) from a mixed diet of freshwater piscivore fishes and terrestrial plants (Roosevelt, 1991; Hermenengildo et al., 2017). Accordingly, these different human food supplies reflected a different habitat for the mosquito hosts as well, with Anopheles gambiae found along both sub-Saharan Africa and the Brazil coastlines (Killeen et al., 2002), in contrast to A. darlingi within the Brazilian and Venezuelan rain forests, A. albimanus along the north Peru coast, and A. pseudopunctipennis in Chile. If malaria had not been eradicated from Chile in 1941 (Ulloa, 1989), standing water after these episodic increased rainfalls of recent El Nin˜os would have also continued to lead
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there to more Chilean malarial epidemics of those mosquito-borne diseases of resident A. pseudopunctipennis. Moreover, clinical malaria now still occurs in Peru (Dharia et al., 2010), both around Iquitos in the Amazon rain forest and along coastal northwest Peru (RosasAguirre et al., 2016) in the seaside city of Tumbes at B3 S, near the border with Ecuador. Unfortunately, during the El Nin˜o of 1998, a resurgence of malaria via the anophelene mosquito vector A. albimanus (Rosas-Aguirre et al., 2016) had instead occurred from the chloroquinine-resistant P. falciparum near Tumbes (Marquino et al., 2003). In 2010, the El Nin˜o of that year (Table 1.4) again resulted next in a similar number of malaria victims in Tumbes (Baldeviano et al., 2015). Yet the surge of malaria episodes there since the 1980s was thought to have been eliminated by the early 2000s (Krisher et al., 2016). I suggest that these ill-health pulmonary cases of both northern Peru and equatorial Ecuador were again other examples of HAB exacerbations of seaside infectious diseases. By 1900, about two-thirds of the world’s supply of quinine was then produced (Taylor, 1945) on Java (Indonesia) plantations, begun in 1866 with seeds of Cinchona ledgeriana, exported illegally by Charles Ledger from Andean Bolivia. There, his native helper was beaten to death by local officials for gathering the seeds and shipping them to London in 1865. When the British Government chose not to buy them, Dutch colonial officials did, effectively forming an Indonesian monopoly on quinine supplies for the next 80 years. During WWII, that previous Asian supply of quinine was curtailed by the Japanese invasion of this island, leading to subsequent war-effort chemical synthesis and testing of 16,000 antimalarial compounds, including chloroquine (Meshnick and Dobson, 2001). Earlier in China during 1596, a herbalist had also recommended use of herbs from quinghao, or sweet wormwood Artemisia annua, to treat both fevers and hemorrhoids. But those effective artemisinin antimalarial drugs were not synthesized, until after WWII (Klayman, 1985; Borrmann et al., 2011). Pragmatically, it took 100 years of organic chemical syntheses from 1918 to 2018 to finally complete a synthetic form of quinine, but with yet no industrial productions—to my knowledge (Rabe and Kindler, 1918; Woodward and Doering, 1944, 1945; Stork et al., 2001; Seeman, 2007; Smith and Williams, 2008; O’Donovan et al., 2018).
5.3 Methylene blue Over the same century, after Guttmann and Ehrlich (1891) first described the positive results of treatment of two of their malaria patients with a thiazine dye, methylene blue, against one of the deadliest species of these protozoan vectors P. falciparum, the efficacy of this treatment of later chloroquine-resistant clones (Wellems and Plowe, 2001; Rengelshausen et al., 2004) of Sierra Leone and Indochina origins had been revisited (Vennerstrom et al., 1995). Subsequent African drug trials of methylene blue and artesunate had also followed (Zoungrana et al., 2008) earlier antimalarial drug trials of plasmoquine in adjacent Liberia during the 1930s (Barber et al., 1932) and of pyrimethamine in 1998 within rural Gambia (von Seidlein et al., 2001). More efficacious applications of other combinations of methylene blue, chloroquine, and artesunate (Meissner et al., 2006; Lu et al., 2018) began
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to combat ubiquitous malaria within Nouna, Burkino Faso, at B1400 km inland from coastal West Africa at Freetown, Sierra Leone. Those combined drugs also impaired formation of the required sexual stages of the initial host P. falciparum (Zoungrana et al., 2008; Couibly, 2009; Gardiner and Trenholme, 2015). Yet in 2013 WHO reported that a third of the nearshore residents of Sierra Leone, i.e., .30,000 coastal victims per 100,000 people, still suffered from malaria. The previous heavy malaria burden of that coastal city had been described over a century earlier as the “white man’s grave”. Moreover, monotherapy of just methylene blue did not completely eradicate 47% of these Plasmodium parasites in Nouna, after only two days of drug treatment (Bountogo et al., 2010), thus requiring more than one magic bullet for their demise there and elsewhere. During 2016, B91% of the 445,000 worldwide deaths of mainly young children, due to malaria, occurred in the sub-Saharan WHO African region, after bites of A. gambiae females.
5.4 Gulf of Guinea’s malaria versus asthma incidences Furthermore, these public health systems of West Africa had recently been stressed two years before during the likely bat-borne Ebola virus epidemic (Zaire ebolavirus) of 201314, when 11,323 people died, including 513 health care workers (Rojek and Horby, 2017). Similarly, along the adjacent Guinea and Sierra Leone coastlines, maximal death incidences due to malaria of 60.771.9 fatalities per 100,000 residents occurred during 2015 in the same coastal regions, where reports of human African trypanosomiasis cases of Trypanosoma brucei gambiense also prevailed (Fig. 5.1). By contrast, recall that the rate of asthma (Table 1.4) was only 3.0% during 2012 in coastal Dakar, Senegal (Hooper et al., 2016), due to the presence of the diatom-dominated offshore eastern boundary Canary Current, i.e., without wind-blown sources of HAB aerosols. I suggest that the presence of asthma-causing HABs along West Africa’s shorelines caused less binary synthesis of parasite-rejecting cytokines of human immune systems, with eventual regional accumulations of infectious disease epicenters, from those of malaria, trypanosomiasis, aspergillosis, tuberculosis, dengue and yellow fevers to Zika and Ebola outbreaks. Within Gambia, Senegal, and the Democratic Republic of Congo, more human deaths from sleeping sickness were then also caused by another set of less potent but still pathogenic Trypanosoma brucei parasites (Fig. 5.1). This toxicity of the protozoan subspecies Trypanosoma brucei gambiensis led to presentment of a different more rapid case of human sleeping sickness in the Gambia colony by May 1901 (Forde, 1902). Following the first diagnosis of malaria but after no response to antimalarial quinine treatments, further examination yielded occurrence of this additional trypanosome in the patient’s blood along coastal northwest Africa (Dutton, 1902). So more than one “magic bullet” was required then and now. Accordingly, the Th2 index of cytokine use during asthma attacks within Senegal and Gambia should have been less in 2012, as indeed studied there earlier (Lienhardt et al., 2002). Under parasite attack in that region, syntheses of binary cytokines were diverted (Lienhardt et al., 2002) from production of Th2 to ameliorate allergenic human responses. Patients then instead made Th1 to deal with a most unfortunate combination of protozoan,
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FIGURE 5.1 Distributions of HAT cases and their protozoan agents. HAT, Human African trypanosomiasis. Source: From Wertheim, H., Horby, P., Woodall, J. (Eds.), 2012. Atlas of Human Infectious Diseases, Wiley-Blackwell, Oxford.
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viral, and fungal parasite invaders of the lungs of those seaside residents. Yet a promise of more antagonist biological weapons in the form of fewer competing dinoflagellate binary HABs lurked within those downstream waters as well. When diatoms outcompeted smaller populations of dinoflagellate HABs, and they in turn diverted human cytokine synthesis to smaller amounts of Th2 compounds to deal with asthmatics, more Th1 could then be used against remaining ciliate vectors of malaria and sleeping sickness. To first make matters worse, the earlier evolution of chronic human pulmonary aspergillosis, due to inhaled fungi and compounded by an immuno-compromised state of the other underlying lung diseases, was very high in parts of Africa by 2005, presented as 42.9 victims per 100,000 residents of both Nigeria and the Democratic Republic of the Congo (Denning et al., 2011). Furthermore, among the many malign mycotoxins produced by Aspergillus fumigatus was gliotoxin (Kamei and Watanabe, 2005; Scharf et al., 2016), as perhaps another malign part of unused “magic bullets” from coastal seas to exacerbate expensive combinations of prophylactic drugs against fungal, protozoan (von Seidlein et al., 2001; Geerligs et al., 2003; Greenwood et al., 2011), bacterial, and viral (Togo and McCracken, 1976) parasites, while undergoing more multidrug prophylaxes of concomitant asthma (Costa de Moura et al., 2002) complications. Gambia, the smallest country in Africa, was captured by the Portuguese in 1455 for use as a river port in the Atlantic slave trade. It was otherwise surrounded by Senegal, with an asthma incidence of 3.0% in its seaside capital of Dakar during 2012 (Hooper et al., 2016). Moreover, during 19902008, Senegalese asthmatic children also had two- to fourfold less resistance to malarial parasites P. falicarpum (Herrant et al., 2013), suggesting another inverse relationship between possible binary human responses to allergens and parasites—mediated by cytokine syntheses (MacDonald et al., 2001; Yazdanbakhsh et al., 2002; Lienhardt et al., 2002). Whereas, the mean asthma rate in downstream seaside cities of Abidjan, Accra, and Lagos was 10.8% during 19712001 (Table 1.4), the malarial death rates were a smaller mean of 41.7 per 100,000 occupants, with evidently more focus on syntheses of human Th1 cytokines. Yet, conversely, the mean rate of TB in 2015 was 163 victims per 100,000 residents within Gambia, Senegal, and Guinea, or just B76% of the average TB incidence of 213 victims per 100,000 residents in Ivory Coast, Ghana, and Nigeria, where both the dinoflagellate HAB and Saharan silicon dust exacerbants of TB severities were more abundant (see Chapter 6: Future numerical consiliences).
5.5 Ivory Coast’s phytoplankton succession at Abidjan During 1980, when coal production was just B15% of that fossil fuel harvest in 1958 (Odesola et al., 2013), a blowout of the no. 5 Nigerian well of the Funiwa oil field dispersed B3.2 3 104 m3 of crude oil throughout the Gulf of Guinea during that one event. Cumulatively over 19582010, petrochemical loadings to the Niger River Delta amounted to B17.6 3 105 m3 oil, in contrast to B7.8 3 105 m3 oil from the Deepwater Horizon blowout
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in the northern GOM (Walsh et al., 2015, 2016). As part of global (Table 1.2) and regional long-term trends, like that off South Africa (Verheye et al., 1998), the downstream zooplankton biomass declined twofold during 1981 on the shelf off Ghana, compared to their stocks there in 1969 (Wiafe et al., 2008). By then, hotly debated (Longhurst, 2007) overfishing of both piscivores and zooplanktivores, in a now familiar trophic cascade response (Pauly et al., 1998) had also begun in 1970 (Cury et al., 2000; Koranteng, 2001; Binet and Marchal, 1993). Once overfishing of piscivores by 1973 led to high stocks of zooplantivore fishes Salix aurita and low biomass of zooplankton in the Gulf of Guinea, with subsequent relaxation of grazing pressures on HABs, greater onshore fluxes of marine HAB asthma triggers would have occurred during the seasonal summer southwest African monsoons. For example, the zooplankton biomass off the Ivory Coast also declined B2-fold there during 196974 (Binet and Marchal, 1993), as expected from the concurrent Ghana time series over the same time period. Yet off Abidjan, Ivory Coast, where local winds induced seasonal upwelling in addition to far-field forcing (Colin, 1988; Houghton, 1989; Longhurst, 1993) of sea spray, the summer temperatures at a depth of 10 m on the 25-m isobath had remained a seasonal minimum of B19 C from 1969 to 1974 (Binet and Marchal, 1993), indicating no change in the rate of coastal upwelling. Thus, presumably any changes of these local plankton food webs to alternative stable equilibrium states (Lewontin, 1969; Scheffer et al., 2001; Scheffer and Carpenter, 2003; Naselli-Flores et al., 2003) were in response to alterations of top-down predation demands, not climatic changes of either vertical mixing of bottom-up nutrient controls or temperature modulations of plankton metabolic rates. However, farther offshore in the Gulf of Guinea, the waters were consistently warmer over the last half century (Odekunle and Eludoyin, 2008). The nutrient stocks there were also less (Voituriez and Herbland, 1979; Le Borgne, 1981) with an N/P ratio of B10 (Oudot and Morin, 1987), favoring colonial and intracellular nitrogen-fixers (Westberry and Siegel, 2006; Foster et al., 2009) and their toxic HAB associates, upon nutrient transfers from diazotrophs to dinoflagellates. Indeed, a subsequent satellite analysis of ocean color data during 19982003 suggested (Gregg et al., 2005) a modest increase of total phytoplankton biomass over this 5-year period in the northwest Gulf of Guinea, where Trichodesmium was also observed in 2005 (John et al., 2002). Consequently, the frequency of hospital admissions for pulmonary afflictions at the seashore in Accra, Ghana, was already 9.1% before 1972 (Anima and Edoo, 1972). By 1995, the prevalence of asthma among school children of the adjacent Ivory Coast had increased to 16% (Asher et al., 1998), with another increment to 18.2% in Abidjan during 2001 (Ait-Khaled et al., 2007), indicative of in situ HAB population successes and onshore transmissions of their aerosols to human victims. Moreover, during JuneJuly 1970 off the Ivory Coast, a very large bloom of dinoflagellates was also then observed (Dardonneau, 1970), i.e., a HAB of Gymnodinium sanguineum, aka G. splendens, Akashiwo sanguinea. It served as a harbinger of other future ungrazed HABs of the Gulf of Guinea. Although A. sanguinea was presumed at that time to be a nontoxic dinoflagellate, it has been subsequently implicated in the mass mortalities of seabirds, forming foam at the sea surface (Jessup et al., 2009), and was a dominant resident of the Indian River Lagoon on the east coast of Florida (Badylak and Phlips, 2004).
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Earlier, during 196568 on the downstream continental shelf off Abidjan, along the northwest sector of the Gulf of Guinea (Reyssac, 1966a,b; Dardonneau, 1971), Gymnodinium spp. and presumably Karenia and Ostreopsis spp., had been prior cryptic members of the phytoplankton community, fueled by frequent occurrences of diazotroph “red water” blooms of Trichodesmium thiebautii along the adjacent upstream Sierra Leone coastline (Aleem, 1980). Nigeria was one of Africa’s largest producers of coal, next to South Africa, such that previous residents of Nigeria and their neighbors, as well as inhabitants of Natal, may have also been subject to inadvertent mercury poisonings via coal burnings, rainfall of inorganic mercury aerosols, and marine sediment bacterial conversions to MeHg. Thus, during 1958, when Nigerian oil fields were first exploited, coal production of this other fossil fuel (Odesola et al., 2013) was actually threefold greater than that of South Africa in 2010. Accordingly, greater mercury pollution may have also prevailed earlier in the adjacent Gulf of Guinea, despite the absence of chlor-alkalai plants in Nigeria. Indeed, by 1994 as much as 490 ng Hg g21 dw had accumulated within sediments of Ebrie Lagoon in Abidjan (Scheren et al., 2002), as in Mobile Bay, Alabama.
5.6 Ghana’s coastal and inland records Farther east at the 30-m isobath off Tema, Ghana, during December 1973, the NO3/PO4 molar ratio was 1.6 within near-surface waters of 27 C (Anang, 1979)—as a favorable chemophysical habitat for the temperature-constrained, phosphorus-limited nitrogen-fixer Trichodesmium spp.—awaiting arrival of January dust loadings from the Sahara Desert (Sunnu, 2012), with an iron content of B5.6% as Fe2O3 (Adeokun et al., 1989). Like other Saharan dust trajectories, computed atmospheric flow fields (Sunnu, 2012) suggested transits of dust-laden air masses from Chad to Kumasi, Ghana (6 400 N, 1 370 W) within B4 days at westward harmattan speeds of B4 m s21. Seaward along those forward dust trajectories into the Gulf of Guinea, these iron-rich mineral aerosols fertilized Trichodesmium spp. precursors of Karenia and Ostreopsis spp. HABs. Within coastal rain forests of the Ivory Coast, these far-field terrestrial nutrients also supported B50% of the annual production of land plants there at the seashore (Stoorvogel et al., 1997; McTainsh and Strong, 2007). In these nearshore Ghana waters during December 1995, Trichodesmium again dominated the phytoplankton community (John et al., 2002). Earlier in 197374, dinoflagellates off Ghana amounted to 50%90% of the phytoplankton during NovemberMay, compared to 90% diatoms in August (Anang, 1979). Moreover, the salinities of these near-surface waters off Tema in December 1973 were B35.2, when nitrogen-fixers were presumably present then as well, compared to B34.4 during the June runoff and B35.9 during the SeptemberOctober upwelling of that year (Anang, 1979). In comparison, asthma attacks among seaside inhabitants of Accra were 9.1% in 1971 (Anima and Edoo, 1972), while 240 km inland from the Ghana coast in Kumasi, asthma incidence was just 3.1% in 1993 (Addo-Yobo et al., 2007), despite at times overlying plumes of Saharan dust (Afeti and Resch, 2000).
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By contrast, when diazotrophs were absent—not using dissolved dinitrogen gas—these riverine and slope supplies of the other nitrate source of “new nitrogen” instead favored faster growing diatoms on the Ghana shelf, with .50% diatoms found between June and October 1973 (Anang, 1979). But such initial bursts of diatoms amounted to only small stocks of phytoplankton. They were presumably under maximal grazing pressures at the start of this local trophic cascade and perhaps nitrogen-limited as well, since Rhizosolenia spp. were found in offshore waters (Reyssac, 1966b). These larger diatoms may then have harbored the nitrogen-fixing endosymbiont Richelia intracellularis (Venrick, 1974), also collected from the Gulf of Guinea (Foster et al., 2009). Similarly, Gymnodinium spp. and the precursor diazotrophs T. thiebautii have been more recently reported from Nigerian coastal waters in the Lagos lagoon and at the mouth of the Niger River but with no recognized human impacts (Akin-Oriola et al., 2006; Ajuzie and Houvenaghel, 2009). At the same time, at least within South African waters, the same genera cooccurred, with more HABs of Karenia spp. (Horstman et al., 1991; Pitcher and Matthews, 1996; Botes et al., 2003a,b).
5.7 LD50 comparisons In terms of toxicity to at least mice bioassays (Table 1.1), the mean lethal dosage at which half the assay population died (LD50) from use of quinine (Abolghasemi et al., 2012) was a very large 850 mg kg21. On the other hand, the LD50 for human inhalation of botulinum A, preventing releases of acetylcholine neurotransmitters from axon endings during bacterial botulism episodes of Clostridium botulinum, was 0.000012 mg kg21 of this most effective neurotoxin (Takahashi et al., 1990). With respect to marine HABs, the LD50 of brevetoxins used in fish-poisoning by Karenia brevis was still 0.180 mg kg21 (Lin et al., 1981; Shimizu et al., 1986; Kimm-Brinson and Ramsdell, 2001). But the other dinoflagellate HAB LD50 of Ostreopsis ovata palytoxin poisons, which drove humans away from European and Indian beaches for pulmonary hospitalizations, was a small 0.000045 mg kg21 (Ramos and Vasconcelos, 2010), i.e., the very toxic poisons of these tychopelagic dinoflagellates of mainly coral reefs were 4000-fold more potent than the pelagic fish-killer K. brevis. Gliotoxins of fungi A. fumigatus (Amitani et al., 1995), arsenate poisons, African trypanocides (Andefiki et al., 2017), and most importantly natural Asian dusts (Hwang et al., 2010) in the form of silicon dioxide had intermediate LD50 of B20 mg kg21 (Table 1.1). More desert dust and coal mine sources of natural quartz crystalline SiO2 had similar LD50 of 45.0 mg kg21 (Yu et al., 2013) of these no longer neglected toxins and carcinogens (Rest, 2002).
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5 Pharmacological antagonist interventions J.J. Walsh Emeritus Distinguished University Professor of Marine Science, University of South Florida, United States
I once read a silly fairy tale, called “The Three Princes of Serendip”: as their Highnesses travelled, they were always making discoveries, by accidents and sagacity, of things which they were not in quest of. Walpole (1754) Similar to the parallel uses of Ephedra spp. in Peru and China, as well as black henbane Hyoscyamus niger (Alizadeh et al., 2014) described in this book earlier within sections on Egypt and Yucatan, Mexico, the pragmatic “whatever worked” approach of these bronchodilators was employed after trial, error, and success histories of multiple afflicted human societies. Before development of synthetic anticholinergic agents in the 1990s, atropine was a natural alkaloid then obtained globally from H. niger after B1833. By 1901, it was first available in asthma cigarettes, as described by Marcel Proust that year in a letter to his mother: Yesterday after I wrote to you I had an attack of asthma and incessant running of the nose, which obliged me to walk all doubled up and light anti-asthma cigarettes at every tobacconist’s I passed (Jackson, 2010). However, like other members of the deadly nightshade Atropa belladonna plant family, H. niger, as well as mandrake Mandragora officinarum and Jimson weed Datura spp., all also contained other alkaloid poisons hyoscine, hyoscyamine, and scopolamine—in addition to atropine. About 3040 seeds of these plants were fatal. Recall that drops of henbone, dripped in his ear, were used to kill the king of Denmark, while he slept in Shakespeare’s play Hamlet. Later other examples of serendipity were the development and uses of penicillin, chloral hydrate, lithium (Ban, 2006), and quinine. The Amazon jungle harbored over 80,000 species of higher plants by 1970, with unknown medical benefits (Schultes, 1969, 1988, 1994, 1999; Prance, 1970, 1972; Schultes and von Reis, 1995; Lawn et al., 2017). But some of those less benign terrestrial drugs and foods there were instead rejected and/or
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used as curare arrow toxins (Table 1.1) by local Amerindians as malign nonstrychnine poisons—but it is the dose alone that makes a poison [Paracelsus (P. von Hohenheim), 1540; Bisset, 1995], like those also discussed here—after blown ashore from the seas.
5.1 Serendipity of penicillin emergence Prior human lung penetrations of parasitic fungi had resulted in subsequent diversions of human biochemical syntheses to form more Th2 cytokines of our immune system (Lucey et al., 1996) to instead deal with allergens rather than Th1 to squelch internal parasite poisons, with at times deadly consequences. Yet, among the 65,000 species of filamentous ascomycete fungal species, some were not benign, such as Penicillium spp. sources of antibiotics. After the serendipitous discovery in 1928 by Alexander Fleming in St. Mary’s Hospital, London, of the antibacterial toxicity of airborne laboratory Penicillium notatum against Staphylococcus (Fleming, 1929), the progress toward Paul Ehrlich’s alternative magic bullet chemotherapy, e.g., use of methylene blue dye (Oz et al., 2011) against malarial protozoan hosts (Guttmann and Ehrlich, 1891), then also accelerated (Lu et al., 2018) as an alternative to quinine therapy. Since the yields of penicillin from P. notatum’s biochemical syntheses were small, however, in 1943 at the Northern Regional Research Laboratory of the Bureau of Agricultural and Industrial Chemistry at Peoria, Illinois, additional fungal sources of penicillin were sought from the surrounding fertile cultivated soils, decomposing fruits and vegetables, and moldy food products of bread, cheese, and cured meats. Another 10-fold greater penicillin producer, Penicillium chrysogenum, compared to P. notatum, was then isolated there from .25 strains of that former group (Raper et al., 1944). Yet in addition to bacteriacaused infectious diseases of pneumonia and tuberculosis, which penicillin and other antibacterials alleviated, unfortunately parasitic protozoans continued to also yield fatal human cases of malaria and sleeping sickness.
5.2 Quinine remedies for other infectious diseases The local Andean drug uses of ephedrine and theophylline to deal with exacerbating allergenic pulmonary maladies and quinine to treat jointly concurrent malaria infections probably began by at least 4500 BCE, when legends say that the Inca Viracocha came out of the Pacific Ocean to found his capital city in the Cuzco Valley. Indeed, other serendipitous discoveries of beneficial pulmonary drugs were also global processes, first documented by the Han Chinese herbalist Shen Nung in his description of the use of Mongolian Ephedra sinica during 2800 BCE in his Pen Ts’ao Kang-mu (Compendium of Materia Medica), written in 1578. Further Ephedra vignettes were recorded: in 60,000-year-old burial sites of Iran; more comments by Pliny of Rome during the first century CE; and then expanded scientific and public audiences over the last few decades (Chevallier, 1996; Fillon, 2003; Schultes and von Reis, 1995). After their 16th-century arrival in the New World, Spanish Jesuit missionaries learned from indigenous Incas of Peru about a medicinal bark, used for the treatment of malarial fevers. With this bark, the Countess of Chincho´n, the wife of the Viceroy of Peru, was supposedly cured in Lima during 1638 of her fever. In any event, the bark from the tree was
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then called Peruvian bark, and the tree was named Cinchona officinalis after the Countess. The medicine from the bark was then known as the antimalarial alkaloid quinine. Along with artemisinins, quinine is still one of the most effective antimalarial drugs available today, despite early signs of quinine resistances of Plasmodium strains by 1907 in Brazil (Da Silva and Benchimol, 2014). In prior pre-Columbian use of quinine by Amerindians in South America, their pest targets may have been the parasites Plasmodium vivax in Venezuela within intermediate mosquito Anopheles darlingi hosts (Gabaldon, 1949), after presumed transits across North and Mesoamerica in other penultimate human hosts. As recently as 1970 on a southcentral Texas ranch, P. vivax infections of children were transmitted by another concurrent mosquito vector Anopheles pseudopunctipennis (Bruce-Chwatt, 1972). By 2010, P. vivax was still .85% of all malarial cases in Venezuela (Grillet et al., 2014) and Mexico (Gonzalez-Ceron et al., 2013). Near the southern border of Mexico with Guatemala in the Mexican State of Chiapas during 201014, larvae of A. darlingi also still occurred in mainly freshwater forest habitats (Villarreal-Trevino et al., 2015). The genome of this species of malarial protozoan parasites was evidently of simian origins in Southeast Asia about 46,00082,000 years ago (Escalante et al., 2005; Cornejo and Escalante, 2006). These microbial data supported the human genetic evidence (Hoffecker et al., 2014) for their anthropogenic transfers of the bacterial TB parasitic counterparts as well, from Northeast Asia to North, Meso-, and South America, albeit over just 14,00050,000 years ago, once Beringia appeared with an implied age of 32,000 years (Guidon and Delibrias, 1986). Other hypotheses recently suggested, however, that similar parasites to P. vivax may have also been hosted by African chimpanzees Pan troglodytes (Liu et al., 2014). Indeed, farther south in Brazil, Plasmodium falciparum of African gene pool origins (Yalcindag et al., 2012) from original primate Gorilla gorilla hosts (Duval et al., 2010), as well as those of chimpanzees, may have instead directly invaded South America multiple times within unwilling human hosts on slave ships during 15011888. Then, B4.9 million African slaves were landed at mainly the coastal cities of Rio de Janeiro and Salazar. Skeletal remains of those Brazilian slaves, with mean herbivore signatures of a del 15N (Bastos et al., 2016) of 18.8 o/oo (Table 1.5), also reflected that of other African slaves before transshipments from South Africa (Cox and Sealy, 1997). Yet, in the Brazilian Amazonas State, the percentage of the total malaria cases in 2009 due to P. falciparum was still only 15.3% (Oliviera-Ferreira et al., 2010), so that the relatively recent African protozoan immigrants had not yet replaced their older Asian competitors for that specific human parasite niche (Rodrigues et al., 2018). At the same time, the extant bone collagen of free Amerindians during B4001300 CE at the mouth of the Amazon River on Marajo Island, near Belem, was instead a mean del 15N of 111.2 o/ oo (Table 1.5) from a mixed diet of freshwater piscivore fishes and terrestrial plants (Roosevelt, 1991; Hermenengildo et al., 2017). Accordingly, these different human food supplies reflected a different habitat for the mosquito hosts as well, with Anopheles gambiae found along both sub-Saharan Africa and the Brazil coastlines (Killeen et al., 2002), in contrast to A. darlingi within the Brazilian and Venezuelan rain forests, A. albimanus along the north Peru coast, and A. pseudopunctipennis in Chile. If malaria had not been eradicated from Chile in 1941 (Ulloa, 1989), standing water after these episodic increased rainfalls of recent El Nin˜os would have also continued to lead
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there to more Chilean malarial epidemics of those mosquito-borne diseases of resident A. pseudopunctipennis. Moreover, clinical malaria now still occurs in Peru (Dharia et al., 2010), both around Iquitos in the Amazon rain forest and along coastal northwest Peru (RosasAguirre et al., 2016) in the seaside city of Tumbes at B3 S, near the border with Ecuador. Unfortunately, during the El Nin˜o of 1998, a resurgence of malaria via the anophelene mosquito vector A. albimanus (Rosas-Aguirre et al., 2016) had instead occurred from the chloroquinine-resistant P. falciparum near Tumbes (Marquino et al., 2003). In 2010, the El Nin˜o of that year (Table 1.4) again resulted next in a similar number of malaria victims in Tumbes (Baldeviano et al., 2015). Yet the surge of malaria episodes there since the 1980s was thought to have been eliminated by the early 2000s (Krisher et al., 2016). I suggest that these ill-health pulmonary cases of both northern Peru and equatorial Ecuador were again other examples of HAB exacerbations of seaside infectious diseases. By 1900, about two-thirds of the world’s supply of quinine was then produced (Taylor, 1945) on Java (Indonesia) plantations, begun in 1866 with seeds of Cinchona ledgeriana, exported illegally by Charles Ledger from Andean Bolivia. There, his native helper was beaten to death by local officials for gathering the seeds and shipping them to London in 1865. When the British Government chose not to buy them, Dutch colonial officials did, effectively forming an Indonesian monopoly on quinine supplies for the next 80 years. During WWII, that previous Asian supply of quinine was curtailed by the Japanese invasion of this island, leading to subsequent war-effort chemical synthesis and testing of 16,000 antimalarial compounds, including chloroquine (Meshnick and Dobson, 2001). Earlier in China during 1596, a herbalist had also recommended use of herbs from quinghao, or sweet wormwood Artemisia annua, to treat both fevers and hemorrhoids. But those effective artemisinin antimalarial drugs were not synthesized, until after WWII (Klayman, 1985; Borrmann et al., 2011). Pragmatically, it took 100 years of organic chemical syntheses from 1918 to 2018 to finally complete a synthetic form of quinine, but with yet no industrial productions—to my knowledge (Rabe and Kindler, 1918; Woodward and Doering, 1944, 1945; Stork et al., 2001; Seeman, 2007; Smith and Williams, 2008; O’Donovan et al., 2018).
5.3 Methylene blue Over the same century, after Guttmann and Ehrlich (1891) first described the positive results of treatment of two of their malaria patients with a thiazine dye, methylene blue, against one of the deadliest species of these protozoan vectors P. falciparum, the efficacy of this treatment of later chloroquine-resistant clones (Wellems and Plowe, 2001; Rengelshausen et al., 2004) of Sierra Leone and Indochina origins had been revisited (Vennerstrom et al., 1995). Subsequent African drug trials of methylene blue and artesunate had also followed (Zoungrana et al., 2008) earlier antimalarial drug trials of plasmoquine in adjacent Liberia during the 1930s (Barber et al., 1932) and of pyrimethamine in 1998 within rural Gambia (von Seidlein et al., 2001). More efficacious applications of other combinations of methylene blue, chloroquine, and artesunate (Meissner et al., 2006; Lu et al., 2018) began
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to combat ubiquitous malaria within Nouna, Burkino Faso, at B1400 km inland from coastal West Africa at Freetown, Sierra Leone. Those combined drugs also impaired formation of the required sexual stages of the initial host P. falciparum (Zoungrana et al., 2008; Couibly, 2009; Gardiner and Trenholme, 2015). Yet in 2013 WHO reported that a third of the nearshore residents of Sierra Leone, i.e., .30,000 coastal victims per 100,000 people, still suffered from malaria. The previous heavy malaria burden of that coastal city had been described over a century earlier as the “white man’s grave”. Moreover, monotherapy of just methylene blue did not completely eradicate 47% of these Plasmodium parasites in Nouna, after only two days of drug treatment (Bountogo et al., 2010), thus requiring more than one magic bullet for their demise there and elsewhere. During 2016, B91% of the 445,000 worldwide deaths of mainly young children, due to malaria, occurred in the sub-Saharan WHO African region, after bites of A. gambiae females.
5.4 Gulf of Guinea’s malaria versus asthma incidences Furthermore, these public health systems of West Africa had recently been stressed two years before during the likely bat-borne Ebola virus epidemic (Zaire ebolavirus) of 201314, when 11,323 people died, including 513 health care workers (Rojek and Horby, 2017). Similarly, along the adjacent Guinea and Sierra Leone coastlines, maximal death incidences due to malaria of 60.771.9 fatalities per 100,000 residents occurred during 2015 in the same coastal regions, where reports of human African trypanosomiasis cases of Trypanosoma brucei gambiense also prevailed (Fig. 5.1). By contrast, recall that the rate of asthma (Table 1.4) was only 3.0% during 2012 in coastal Dakar, Senegal (Hooper et al., 2016), due to the presence of the diatom-dominated offshore eastern boundary Canary Current, i.e., without wind-blown sources of HAB aerosols. I suggest that the presence of asthma-causing HABs along West Africa’s shorelines caused less binary synthesis of parasite-rejecting cytokines of human immune systems, with eventual regional accumulations of infectious disease epicenters, from those of malaria, trypanosomiasis, aspergillosis, tuberculosis, dengue and yellow fevers to Zika and Ebola outbreaks. Within Gambia, Senegal, and the Democratic Republic of Congo, more human deaths from sleeping sickness were then also caused by another set of less potent but still pathogenic Trypanosoma brucei parasites (Fig. 5.1). This toxicity of the protozoan subspecies Trypanosoma brucei gambiensis led to presentment of a different more rapid case of human sleeping sickness in the Gambia colony by May 1901 (Forde, 1902). Following the first diagnosis of malaria but after no response to antimalarial quinine treatments, further examination yielded occurrence of this additional trypanosome in the patient’s blood along coastal northwest Africa (Dutton, 1902). So more than one “magic bullet” was required then and now. Accordingly, the Th2 index of cytokine use during asthma attacks within Senegal and Gambia should have been less in 2012, as indeed studied there earlier (Lienhardt et al., 2002). Under parasite attack in that region, syntheses of binary cytokines were diverted (Lienhardt et al., 2002) from production of Th2 to ameliorate allergenic human responses. Patients then instead made Th1 to deal with a most unfortunate combination of protozoan,
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FIGURE 5.1 Distributions of HAT cases and their protozoan agents. HAT, Human African trypanosomiasis. Source: From Wertheim, H., Horby, P., Woodall, J. (Eds.), 2012. Atlas of Human Infectious Diseases, Wiley-Blackwell, Oxford.
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viral, and fungal parasite invaders of the lungs of those seaside residents. Yet a promise of more antagonist biological weapons in the form of fewer competing dinoflagellate binary HABs lurked within those downstream waters as well. When diatoms outcompeted smaller populations of dinoflagellate HABs, and they in turn diverted human cytokine synthesis to smaller amounts of Th2 compounds to deal with asthmatics, more Th1 could then be used against remaining ciliate vectors of malaria and sleeping sickness. To first make matters worse, the earlier evolution of chronic human pulmonary aspergillosis, due to inhaled fungi and compounded by an immuno-compromised state of the other underlying lung diseases, was very high in parts of Africa by 2005, presented as 42.9 victims per 100,000 residents of both Nigeria and the Democratic Republic of the Congo (Denning et al., 2011). Furthermore, among the many malign mycotoxins produced by Aspergillus fumigatus was gliotoxin (Kamei and Watanabe, 2005; Scharf et al., 2016), as perhaps another malign part of unused “magic bullets” from coastal seas to exacerbate expensive combinations of prophylactic drugs against fungal, protozoan (von Seidlein et al., 2001; Geerligs et al., 2003; Greenwood et al., 2011), bacterial, and viral (Togo and McCracken, 1976) parasites, while undergoing more multidrug prophylaxes of concomitant asthma (Costa de Moura et al., 2002) complications. Gambia, the smallest country in Africa, was captured by the Portuguese in 1455 for use as a river port in the Atlantic slave trade. It was otherwise surrounded by Senegal, with an asthma incidence of 3.0% in its seaside capital of Dakar during 2012 (Hooper et al., 2016). Moreover, during 19902008, Senegalese asthmatic children also had two- to fourfold less resistance to malarial parasites P. falicarpum (Herrant et al., 2013), suggesting another inverse relationship between possible binary human responses to allergens and parasites—mediated by cytokine syntheses (MacDonald et al., 2001; Yazdanbakhsh et al., 2002; Lienhardt et al., 2002). Whereas, the mean asthma rate in downstream seaside cities of Abidjan, Accra, and Lagos was 10.8% during 19712001 (Table 1.4), the malarial death rates were a smaller mean of 41.7 per 100,000 occupants, with evidently more focus on syntheses of human Th1 cytokines. Yet, conversely, the mean rate of TB in 2015 was 163 victims per 100,000 residents within Gambia, Senegal, and Guinea, or just B76% of the average TB incidence of 213 victims per 100,000 residents in Ivory Coast, Ghana, and Nigeria, where both the dinoflagellate HAB and Saharan silicon dust exacerbants of TB severities were more abundant (see Chapter 6: Future numerical consiliences).
5.5 Ivory Coast’s phytoplankton succession at Abidjan During 1980, when coal production was just B15% of that fossil fuel harvest in 1958 (Odesola et al., 2013), a blowout of the no. 5 Nigerian well of the Funiwa oil field dispersed B3.2 3 104 m3 of crude oil throughout the Gulf of Guinea during that one event. Cumulatively over 19582010, petrochemical loadings to the Niger River Delta amounted to B17.6 3 105 m3 oil, in contrast to B7.8 3 105 m3 oil from the Deepwater Horizon blowout
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in the northern GOM (Walsh et al., 2015, 2016). As part of global (Table 1.2) and regional long-term trends, like that off South Africa (Verheye et al., 1998), the downstream zooplankton biomass declined twofold during 1981 on the shelf off Ghana, compared to their stocks there in 1969 (Wiafe et al., 2008). By then, hotly debated (Longhurst, 2007) overfishing of both piscivores and zooplanktivores, in a now familiar trophic cascade response (Pauly et al., 1998) had also begun in 1970 (Cury et al., 2000; Koranteng, 2001; Binet and Marchal, 1993). Once overfishing of piscivores by 1973 led to high stocks of zooplantivore fishes Salix aurita and low biomass of zooplankton in the Gulf of Guinea, with subsequent relaxation of grazing pressures on HABs, greater onshore fluxes of marine HAB asthma triggers would have occurred during the seasonal summer southwest African monsoons. For example, the zooplankton biomass off the Ivory Coast also declined B2-fold there during 196974 (Binet and Marchal, 1993), as expected from the concurrent Ghana time series over the same time period. Yet off Abidjan, Ivory Coast, where local winds induced seasonal upwelling in addition to far-field forcing (Colin, 1988; Houghton, 1989; Longhurst, 1993) of sea spray, the summer temperatures at a depth of 10 m on the 25-m isobath had remained a seasonal minimum of B19 C from 1969 to 1974 (Binet and Marchal, 1993), indicating no change in the rate of coastal upwelling. Thus, presumably any changes of these local plankton food webs to alternative stable equilibrium states (Lewontin, 1969; Scheffer et al., 2001; Scheffer and Carpenter, 2003; Naselli-Flores et al., 2003) were in response to alterations of top-down predation demands, not climatic changes of either vertical mixing of bottom-up nutrient controls or temperature modulations of plankton metabolic rates. However, farther offshore in the Gulf of Guinea, the waters were consistently warmer over the last half century (Odekunle and Eludoyin, 2008). The nutrient stocks there were also less (Voituriez and Herbland, 1979; Le Borgne, 1981) with an N/P ratio of B10 (Oudot and Morin, 1987), favoring colonial and intracellular nitrogen-fixers (Westberry and Siegel, 2006; Foster et al., 2009) and their toxic HAB associates, upon nutrient transfers from diazotrophs to dinoflagellates. Indeed, a subsequent satellite analysis of ocean color data during 19982003 suggested (Gregg et al., 2005) a modest increase of total phytoplankton biomass over this 5-year period in the northwest Gulf of Guinea, where Trichodesmium was also observed in 2005 (John et al., 2002). Consequently, the frequency of hospital admissions for pulmonary afflictions at the seashore in Accra, Ghana, was already 9.1% before 1972 (Anima and Edoo, 1972). By 1995, the prevalence of asthma among school children of the adjacent Ivory Coast had increased to 16% (Asher et al., 1998), with another increment to 18.2% in Abidjan during 2001 (Ait-Khaled et al., 2007), indicative of in situ HAB population successes and onshore transmissions of their aerosols to human victims. Moreover, during JuneJuly 1970 off the Ivory Coast, a very large bloom of dinoflagellates was also then observed (Dardonneau, 1970), i.e., a HAB of Gymnodinium sanguineum, aka G. splendens, Akashiwo sanguinea. It served as a harbinger of other future ungrazed HABs of the Gulf of Guinea. Although A. sanguinea was presumed at that time to be a nontoxic dinoflagellate, it has been subsequently implicated in the mass mortalities of seabirds, forming foam at the sea surface (Jessup et al., 2009), and was a dominant resident of the Indian River Lagoon on the east coast of Florida (Badylak and Phlips, 2004).
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Earlier, during 196568 on the downstream continental shelf off Abidjan, along the northwest sector of the Gulf of Guinea (Reyssac, 1966a,b; Dardonneau, 1971), Gymnodinium spp. and presumably Karenia and Ostreopsis spp., had been prior cryptic members of the phytoplankton community, fueled by frequent occurrences of diazotroph “red water” blooms of Trichodesmium thiebautii along the adjacent upstream Sierra Leone coastline (Aleem, 1980). Nigeria was one of Africa’s largest producers of coal, next to South Africa, such that previous residents of Nigeria and their neighbors, as well as inhabitants of Natal, may have also been subject to inadvertent mercury poisonings via coal burnings, rainfall of inorganic mercury aerosols, and marine sediment bacterial conversions to MeHg. Thus, during 1958, when Nigerian oil fields were first exploited, coal production of this other fossil fuel (Odesola et al., 2013) was actually threefold greater than that of South Africa in 2010. Accordingly, greater mercury pollution may have also prevailed earlier in the adjacent Gulf of Guinea, despite the absence of chlor-alkalai plants in Nigeria. Indeed, by 1994 as much as 490 ng Hg g21 dw had accumulated within sediments of Ebrie Lagoon in Abidjan (Scheren et al., 2002), as in Mobile Bay, Alabama.
5.6 Ghana’s coastal and inland records Farther east at the 30-m isobath off Tema, Ghana, during December 1973, the NO3/PO4 molar ratio was 1.6 within near-surface waters of 27 C (Anang, 1979)—as a favorable chemophysical habitat for the temperature-constrained, phosphorus-limited nitrogen-fixer Trichodesmium spp.—awaiting arrival of January dust loadings from the Sahara Desert (Sunnu, 2012), with an iron content of B5.6% as Fe2O3 (Adeokun et al., 1989). Like other Saharan dust trajectories, computed atmospheric flow fields (Sunnu, 2012) suggested transits of dust-laden air masses from Chad to Kumasi, Ghana (6 400 N, 1 370 W) within B4 days at westward harmattan speeds of B4 m s21. Seaward along those forward dust trajectories into the Gulf of Guinea, these iron-rich mineral aerosols fertilized Trichodesmium spp. precursors of Karenia and Ostreopsis spp. HABs. Within coastal rain forests of the Ivory Coast, these far-field terrestrial nutrients also supported B50% of the annual production of land plants there at the seashore (Stoorvogel et al., 1997; McTainsh and Strong, 2007). In these nearshore Ghana waters during December 1995, Trichodesmium again dominated the phytoplankton community (John et al., 2002). Earlier in 197374, dinoflagellates off Ghana amounted to 50%90% of the phytoplankton during NovemberMay, compared to 90% diatoms in August (Anang, 1979). Moreover, the salinities of these near-surface waters off Tema in December 1973 were B35.2, when nitrogen-fixers were presumably present then as well, compared to B34.4 during the June runoff and B35.9 during the SeptemberOctober upwelling of that year (Anang, 1979). In comparison, asthma attacks among seaside inhabitants of Accra were 9.1% in 1971 (Anima and Edoo, 1972), while 240 km inland from the Ghana coast in Kumasi, asthma incidence was just 3.1% in 1993 (Addo-Yobo et al., 2007), despite at times overlying plumes of Saharan dust (Afeti and Resch, 2000).
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By contrast, when diazotrophs were absent—not using dissolved dinitrogen gas—these riverine and slope supplies of the other nitrate source of “new nitrogen” instead favored faster growing diatoms on the Ghana shelf, with .50% diatoms found between June and October 1973 (Anang, 1979). But such initial bursts of diatoms amounted to only small stocks of phytoplankton. They were presumably under maximal grazing pressures at the start of this local trophic cascade and perhaps nitrogen-limited as well, since Rhizosolenia spp. were found in offshore waters (Reyssac, 1966b). These larger diatoms may then have harbored the nitrogen-fixing endosymbiont Richelia intracellularis (Venrick, 1974), also collected from the Gulf of Guinea (Foster et al., 2009). Similarly, Gymnodinium spp. and the precursor diazotrophs T. thiebautii have been more recently reported from Nigerian coastal waters in the Lagos lagoon and at the mouth of the Niger River but with no recognized human impacts (Akin-Oriola et al., 2006; Ajuzie and Houvenaghel, 2009). At the same time, at least within South African waters, the same genera cooccurred, with more HABs of Karenia spp. (Horstman et al., 1991; Pitcher and Matthews, 1996; Botes et al., 2003a,b).
5.7 LD50 comparisons In terms of toxicity to at least mice bioassays (Table 1.1), the mean lethal dosage at which half the assay population died (LD50) from use of quinine (Abolghasemi et al., 2012) was a very large 850 mg kg21. On the other hand, the LD50 for human inhalation of botulinum A, preventing releases of acetylcholine neurotransmitters from axon endings during bacterial botulism episodes of Clostridium botulinum, was 0.000012 mg kg21 of this most effective neurotoxin (Takahashi et al., 1990). With respect to marine HABs, the LD50 of brevetoxins used in fish-poisoning by Karenia brevis was still 0.180 mg kg21 (Lin et al., 1981; Shimizu et al., 1986; Kimm-Brinson and Ramsdell, 2001). But the other dinoflagellate HAB LD50 of Ostreopsis ovata palytoxin poisons, which drove humans away from European and Indian beaches for pulmonary hospitalizations, was a small 0.000045 mg kg21 (Ramos and Vasconcelos, 2010), i.e., the very toxic poisons of these tychopelagic dinoflagellates of mainly coral reefs were 4000-fold more potent than the pelagic fish-killer K. brevis. Gliotoxins of fungi A. fumigatus (Amitani et al., 1995), arsenate poisons, African trypanocides (Andefiki et al., 2017), and most importantly natural Asian dusts (Hwang et al., 2010) in the form of silicon dioxide had intermediate LD50 of B20 mg kg21 (Table 1.1). More desert dust and coal mine sources of natural quartz crystalline SiO2 had similar LD50 of 45.0 mg kg21 (Yu et al., 2013) of these no longer neglected toxins and carcinogens (Rest, 2002).
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