Chapter 1: Introduction

• “Japan had experienced outbreaks of drug resistant bacteria in the 1950s, but at the time these epidemics were little noticed in the West.” (Davies 1995)
• “the forty days that ships had to wait outside the city of Venice to be sure they were free of plague” (Mackowiak and Sehdev 2002; Maglen 2003)
• Although the standard story is still that plague is mostly spread by rats and rat fleas, there is a lively debate about whether transmission among humans mediated by human ectoparasites (especially lice) may have been important in some plague epidemics (Dean et al. 2018). Plague can also spread pneumonically, directly from human to human, by coughing (this form of plague is extremely virulent).
• “Smallpox is thought to have moved from rodents into humans at least 16,000 years ago”. The earliest direct evidence of smallpox in humans (as opposed to inferences from phylogenetic patterns) is approx. 1000 BCE (Mühlemann et al. 2020)
• “measles probably moved from cattle to humans when humans first started to live in large cities”. Current date on the divergence between measles and rinderpest is approximately 600 BCE (Düx et al. 2020); the disease was first unambiguously described by the Arabic physician Abu Bakr Mohammad Ibn Zakariya al-Razi (Rhazes) around 900 AD.
• “A small number of mutations in the West Nile virus (WNV) that arose in the late 1990s made it far more lethal to birds and mice” (Audsley et al. 2011)
• “scientists have found antibiotic resistance genes similar to modern variants in DNA extracted from 30,000-year-old frozen soil” (D’Costa et al. 2011)
• “some biologists have pointed out that mixing between spatially separated populations can encourage virulence, although so far there are no verified real-world examples of this phenomenon” (Cressler et al. 2016; Granato et al. 2018; Nørgaard et al. 2021; Boots and Mealor 2007; Boots, Hudson, and Sasaki 2004). This continues to be a contentious area. Some potential examples are the emergence of virulence in rabbit haemorrhagic disease, the spread of peste des petit ruminants (PPR, a close relative of rinderpest), and the evolution of Yersinia pestis (the plague bacteria) from Y. pseudotuberculosis. However, explanations of virulence shifts in the wild are likely to remain circumstantial.

Chapter 2: transmission at different scales.

• In some unusual cases, anthrax spores can be spread by flies (Blackburn et al. 2010); airborne spread in the wild is unlikely (Turnbull et al. 1998), but it has been spread anthropogenically from a Soviet weapons lab (Leitenberg 1992)
• Although the basic biology of the sickle cell trait has been known since the 1950s, we are still learning about the mechanisms by which it promotes resistance (Williams et al. 2005) and tolerance (Ferreira et al. 2011; S. M. Taylor, Cerami, and Fairhurst 2013)
• Neckties as fomites (Frei 2015; Campion 2016; Kandel 2011; McGovern et al. 2010; Nurkin 2004)
• On the GARKI program to eliminate malaria and the dangers of focusing on a single control method (Gladwell 2002)
• Assessing the Imperial College COVID-19 model: (Adam 2020; van Basshuysen and White 2021; Biggs and Littlejohn 2021)

Chapter 3: influenza

• Assessing influenza mortality (Paget et al. 2019; Simonsen et al. 2013; Spreeuwenberg, Kroneman, and Paget 2018)
• Gain of function (Rozo and Gronvall 2015; Warmbrod, Montague, and Gronvall 2021; Dance 2021; Gillum and Moritz 2021)

Chapter 4: HIV

•  “disease agents such as the fungi Pneumocystis jirovecii”: this pathogen was previously thought to be a protozoan rather than a fungus, and was called Pneumocystis carinii https://www.cdc.gov/fungal/diseases/pneumocystis-pneumonia/index.html
• “intravenous (IV) drug users share needles for economic or social reasons” (N. J. Kim et al. 2015)
• “HIV is incredibly variable”. Here we left out discussion of the spatial variability of HIV strains, which can useful in tracking the geographic spread of the virus. It’s not entirely clear how much this geographic variation contributes to the difficulty of treating and controlling HIV, although there are some suggestions that the original RV-114 vaccine trial in Thailand (which showed higher efficacy than subsequent trials) was in a location with relatively little HIV variation, and that later (less effective) trials were in locations with more variation. https://www.hiv.lanl.gov/content/sequence/HIV/CRFs/CRFs.html (Paraskevis et al. 2009)
• “inactive copies of HIV can lurk in our cells and later become reactivated” (Traylen et al. 2011). The technical term for a copy of the HIV genome that has been integrated into the host (human) genome is a provirus. Other retroviruses such a human T-lymphotropic virus (HTLV) can also lurk in this way. Herpesviruses and tuberculosis bacteria can also remain latent for long periods of time, although the biological mechanisms, and where they lurk in the body, are different.
• “the CCR5-Δ32 mutation has been found in DNA from ancient human remains” (Hummel et al. 2005).
• “the result of genetic drift rather than natural selection”. The origins and history of the CCR5-Δ32 allele have been strenuously debated among population geneticists, mathematical modelers, and historians. Various hypotheses about the importance of the Black Death or smallpox in selecting for the CCR5-Δ32 have been proposed, and disposed, along the way (Bouwman et al. 2017; Cohn and Weaver 2006; Duncan, Scott, and Duncan 2005; Faure and Royer-Carenzi 2008; Novembre and Han 2012; Novembre, Galvani, and Slatkin 2005; Galvani and Novembre 2005)
• “Other, less well-known genes conferring resistance to HIV” (McLaren and Carrington 2015; Regoes et al. 2014)
• “highly active antiretroviral therapies” (Eggleton and Nagalli 2022)
• “through a process called recombination” (Cromer et al. 2016)
• “an infected cell dies in about a day, and given HIV virion in the bloodstream survives for less than two hours” (Simon and Ho 2003) say “[t]he half-life of productively infected CD4+ T lymphocytes is approximately 17 hours; the turnover rate of virions is even faster, with a half-life of less than one hour.” If the half-life of a cell (the time until 50% of initially infected cells die) is t1/2, then the expected lifetime is t1/2/ln(2) ≈ 1.42 t1/2.
• “the best HIV vaccines tested so far only prevented disease 60% of the time after 1 year” (J. Kim et al. 2021)
• “many may never become symptomatic” (Ortblad et al. 2019)
• “allow their immune systems to suppress HIV concentrations to low level without the use of drugs” (Gupta et al. 2020; Ndung’u, McCune, and Deeks 2019)
• “London patient” status 2023 (Gupta et al. 2020; Mouzo 2023)
• “Another reason to try to cure HIV rather than relying on HAART is that about 50% of people living with HIV suffer from some level of neurological impairment (HIV-Associated Neurocognitive Disorder, or HAND), even when HAART is working to lower their virus load to undetectable levels.”: see (Alford and Vera 2018)
• “further set back by disruption of health services due to COVID-19”(Bain, Nkoke, and Noubiap 2017; Uwishema et al. 2022; Yusuff Adebayo et al. 2021) https://www.unaids.org/en/resources/campaigns/HowAIDSchangedeverything/factsheet
• “though the original zoonotic event (the jump from chimpanzees into humans) may have occurred earlier”: we can gain some insight into the spread of HIV in sub-Saharan Africa by looking at the parallel spread of hepatitis C, another sexually transmitted virus (Pépin 2021; Markov et al. 2009) 
• “a two-step spillover from a shipment of infected Gambian pouched rats from Africa, to prairie dogs reared in captivity for the pet trade, to humans” (Reed et al. 2004)
• “In Africa, human-to-human transmission of Mpox has evolved at least once (likely several times)” (Beer and Rao 2019)                                   
• “helped spread HIV across the rest of the globe” (Giles-Vernick et al. 2013; Sousa et al. 2021)
• “may have facilitated the process of viral adaptation to humans” (Vance 2019). With regards to the theory that contaminated polio virus was the source of HIV (Hooper 1999), Pépin (2021, p. 214) says “there is no documentary evidence that any of these laboratories  manipulated blood or serum in a way or on a scale that could have facilitated the emergence of HIV-1. The Stanleyville laboratory was the only one that used a substantial number of chimpanzees, but we have seen that this is not where HIV-1 originated.”

Chapter 5: Cholera

• “Accordingly, instead of immune evasion, bacteria focus on resistance to host countermeasures”: although it is rare in bacteria, some protozoan parasites do use immune suppression (malaria) or evasion (trypanosomes) (Faria et al. 2022; J. E. Taylor and Rudenko 2006; Sakoguchi and Arase 2022)
• “Cholera serotypes” (Kaper, Morris, and Levine 1995)
• Phage therapy and cholera: (Sulakvelidze, Alavidze, and Morris 2001)
• Cholera and seawater: (Colwell 1996)
• “sari filtration reduced infection rates by 50%”: (Colwell et al. 2003)
• “Death rate in Haiti in first year of outbreak”: http://www.cdc.gov/haiticholera/haiti_cholera.htm
• “Haitian cholera origin not environmental”: (Cravioto et al. 2010)
• “Mechanisms of antibiotic resistance”: (Kitaoka et al. 2011)
• “Multi-antibiotic resistance was gained via the SXT plasmid” during the second and third waves of the 7th pandemic, including invasion of Haiti:(Mutreja et al. 2011)
• “WHO recommendation re vaccines as complement to infrastructure”: (World Health Organization 2018) 
• “Economic burden of cholera”: (Mogasale, Mogasale, and Hsiao 2020)​​

Chapter 6: Malaria

• “poorer educational outcomes in children” (Holding and Snow 2001)
• “in terms of disability-adjusted life years” (Feng et al. 2020) 
• “thanks to control efforts, it had fallen to third place (after HIV/AIDS and tuberculosis” (Vos et al. 2020)
• “could increase economic growth rates by several percentage points, the difference between a struggling economy and a healthy one” (Sarma et al. 2019)
• “human-mosquito-human transmission, as opposed to monkey-mosquito-human transmission, is rare” (Barber et al. 2017; Ruiz Cuenca et al. 2022)
• “and continue to multiply, infecting and destroying red blood cells as the population grows” (Bannister 2001)
• “In cerebral malaria, parasites block blood flow and trigger inflammation, killing untreated patients and often causing brain damage even in patients who are treated and recover” (Idro et al. 2010)
• “although fever does not itself seem to be harmful” (Meremikwu et al. 2012)
• “every other day (tertian: P. vivax and P. ovale) or every three days (quartan: P. malariae and P. falciparum)”. “Quotidian” fever  (recurring daily) is more rarely described, probably falciparum. (these terms are used in magical texts from the Graeco-Roman period, although obviously the authors knew nothing about the biology of malaria …) (Scheidel 2001)
• “Biologists have retrieved ancient DNA from 4,000-year-old Egyptian mummies” (Lalremruata et al. 2013; Nerlich et al. 2008)
• “Malaria is part of a large, complex family of parasites” (Garamszegi 2009; Poinar and Telford 2005; Outlaw and Ricklefs 2011; Ricklefs and Outlaw 2010)        
• “Analyses of the genome of P. falciparum, the most dangerous species of human malaria, suggest that its population expanded greatly about 10,000 years ago”         (Harper and Armelagos 2013; Rougeron, Boundenga, et al. 2022) 
• “have established that P. falciparum is most closely related to a malaria species of gorillas” (Loy et al. 2017)
• “other strains of P. vivax were already circulating there, brought earlier by ocean voyagers from South-East Asia” (Rougeron, Daron, et al. 2022)
• “humans’ adaptive immune systems can also help” (Roberts et al. 1992)
• “Our historical knowledge of malaria begins with humans’ first attempts to consciously defend themselves against malaria”: (Hempelmann and Krafts 2013; Meshnick and Dobson 2001)                           
• “controlling malaria transmission: (Derua et al. 2019) See also studies on specialized water containers that block larval mosquito entry, used more for dengue control since many of the species that transmit dengue are specialized to breed in small bodies of water (De Silva and Marshall 2012; Kitron and Spielman 1989; Fillinger and Lindsay 2006)
• “Indoor residual spraying programmes apply long-lasting insecticide to surfaces in houses where mosquitoes like to land” (Centers for Disease Control 2019)
• “are thought to have led to declines in malaria in the northern US in the late 19th century” (Faust 1951)
• “active brick-making pits, which hold water but tend to have few mosquito-eating predators, providing a perfect habitat for larvae” (Carlson, Byrd, and Omlin 2004)
• “although this may be due to the settlement of humans in forest edges rather than with landscape modification per se” (MacDonald and Mordecai 2019)                 
• “The Global Malaria Eradication Program, which began in 1955 and aimed to eradicate malaria by 1963, encountered all of these problems, and more” (Nájera, González-Silva, and Alonso 2011)                 
• “experiments in flies have shown that DDT resistance does not seem to lower their fecundity, so DDT resistance is likely to persist for a long time” (Rivero et al. 2010; ffrench-Constant and Bass 2017)
• “the evolution of partial resistance in South East Asia, and resistance is beginning to emerge in Africa as well” (Ashley et al. 2014; Balikagala et al. 2021)
• “crash malaria control programme”: technically this is resistance to artemisinin combination therapy (ACT), a multi-drug cocktail including artemisinin, not just resistance to artemisinin itself (Imwong et al. 2017; World Health Organization 2023)         
• “the recently developed RTS,S vaccine, which has recently been deployed in a large-scale pilot study of 10 million doses for children in Ghana, Kenya and Malawi.” (Adepoju 2019; Laurens 2019; Mayer 2020; Olotu et al. 2016; World Health Organization 2021a)                                   
• “Other, possibly more effective, vaccines are under development but have different challenges such as the need for extremely low-temperature storage.” (Garcia et al. 2013)
• Researchers have recently reported promising results from phase 2 trials of the R-21/Matrix-M vaccine - 75% efficacy against clinical malaria (Datoo et al. 2022). There are many hurdles even between phase 2 success and deployment (will the same efficacy be observed in phase-3 trials/in different populations around the world? What are the thermostability/cold chain requirements and cost?), but this is very good news nevertheless.
• “Governments and agencies will have to deploy different combinations of the available tools (source control, residual spraying, bed nets, treatment, and eventually vaccine) in ways that are appropriate to the local situation.”(World Health Organization 2022)

Chapter 7: Amphibian fungus

• “The recent decline in honeybees, the causes of which are still hotly debated but which include pathogens, has severely compromised the California almond crops they pollinate; chronic wasting disease in wild elk threatens to cost Canadian elk farmers millions of dollars.” Abalone are another example of economic impacts of infectious disease in animals (Ghazoul 2007; Lafferty et al. 2015; Argue et al. 2007)                                   
• “Sea lice. a parasitic crustacean of fish that thrives in high-density salmon farms, may be spilling over to harm wild salmon populations.”  (Shephard and Gargan 2021; Marty, Saksida, and Quinn 2010; Lafferty et al. 2015; Krkosek et al. 2006)                                   
• “waterbirds may act as dispersal vectors”(Garmyn et al. 2012; Burrowes and De la Riva 2017; Kolby et al. 2015)                                   
• “Some experiments have suggested that Bd may also produce toxins that contribute to mortality.” (Carver, Bell, and Waldman 2010; Blaustein et al. 2005; Fites et al. 2013; Salla et al. 2018; Voyles et al. 2009; 2007; McMahon et al. 2013; Campbell et al. 2012; Voyles et al. 2012) 
• “Since the Out of Africa hypothesis was first proposed, researchers have detected Bd on the skin of an American bullfrog (Lithobates catesbeianus, another Bd-tolerant species) collected in 1928, in California, and from an even earlier collection of frogs from the Atlantic forest of Brazil going all the way back to 1894.” (Basanta et al. 2021; Burrowes and De la Riva 2017; Basanta et al. 2021; Padgett-Flohr and Ii 2009; Amorim et al. 2019; Becker et al. 2016)                                   
• “From this ancient gene pool, a global pandemic lineage emerged from Asia between 50 to 120 years ago, spreading worldwide probably by means of commercially traded, tolerant species like American bullfrogs and Xenopus.” (Fisher and Garner 2020)                                   
• “Researchers have discovered that exposing some amphibians to dead Bd in the lab can give them partial resistance to Bd, but it is unclear whether this finding can be used to develop a practical disease-fighting strategy.” (McMahon et al. 2014; Stice and Briggs 2010)                                   
• “biologists are trying to manage a broad range of threats – volcanic activity, overhunting, invasive species, pollution, and development – in addition to Bd.” (Bosch et al. 2015; Charles 2021; Jameson et al. 2019)

Chapter 8 SARS-CoV-2/COVID-19

• “better care can save an infected person from dying” (lowering the case fatality rate, or CFR): this argument applies both at the individual level (people in places with generally better health care are less likely to die from COVID-19) and at the population level (when COVID-19 runs rampant in a population the entire health care system may break down, so that people die who could have been saved if the epidemic had been controlled to lower levels)
• “Zambia reported fewer than 4,000 COVID-19 deaths in the entire pandemic (to June 2022), but excess mortality for 2021 alone represented 80,000 deaths”  (Wang et al. 2022)
• “Other infectious diseases have hurt or killed more people in total: current estimates of the total worldwide mortality due to COVID-19 (up to the end of 2021) are in the range of 20 million people, while the HIV pandemic has killed 36 million people; the 1918-1920 flu pandemic killed 18 million people in a world with only a quarter the size of today’s human population.” (Wang et al. 2022; World Health Organization 2021b; Spreeuwenberg, Kroneman, and Paget 2018)         
• “suggests that the COVID-19 pandemic actually started from two separate zoonotic events in late November or early December of 2019” (Pekar et al. 2022)                           
• “further sampling may eventually change our conclusions about SARS-CoV-2’s origin”: screening forest workers in Myanmar for antibodies to sarbecoviruses (the subfamily including SARS-CoV-1 and SARS-CoV-2 prior to the COVID-19 pandemic) found that 12% of them had been exposed to these viruses (Evans et al. 2023)
• “contact tracing breaks down as soon as a disease spreads widely, because the number of cases and the number of contacts who must be contacted and observed or isolated snowballs beyond the ability of a limited number of contact tracing personnel to keep up.”(Otto 2020)
• “already starting a few weeks later. Nearly all of the time between the emergence of COVID-19 and the availability of vaccines starting in December 2020 was taken by studies of vaccine safety and efficacy required before public health agencies could approve the vaccines for emergency use, rather than vaccine production itself.” (Rosa et al. 2021)

Chapter 9 Looking ahead

• “Availability and use of Ebola vaccines in Africa”: https://www.who.int/news-room/questions-and-answers/item/ebola-vaccines
• Definition of and complications from microcephaly: https://www.cdc.gov/ncbddd/birthdefects/microcephaly.html
• Rates and number of cases of microcephaly in Brazil as a probable result of Zika (Peiter et al. 2020)
• History of zika (Wikan and Smith 2016)
• Guillain-Barré syndrome background: https://www.who.int/news-room/fact-sheets/detail/guillain-barré-syndrome
• “retrospective analysis revealed that there had indeed been an increase in microcephalic births during the Zika outbreak in French Polynesia” (Cauchemez et al. 2016) 

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