Infectious Madness: The Surprising Science of How We "Catch" Mental Illness

CHAPTER 7

Tropical Madness: Infection and Neglect in the Developing World

The idea that some lives matter less is the root of all that’s wrong with the world.

—PAUL FARMER, MD, COFOUNDER OF PARTNERS IN HEALTH

Acanit sat silent and unmoving on the bare and dented metal chair. It contrasted with her well-tailored knit suit, which Dr. Nabwire could not help thinking must be uncomfortably hot in the stifling air of the clinic’s treatment room. Acanit’s husband, Felix, had been gently bouncing their eight-month-old daughter, Dindi, on his lap, but he now stopped to complain, “My wife has been like this off and on for weeks. Now, she hardly speaks a word to me or our daughter. I don’t know what she’s thinking; she never acted this way before. Mentally, she has always been very strong; she is an exceptionally intelligent woman, but I don’t know her anymore. What’s wrong?” he demanded. As his voice rose in pitch and volume, he stared intently at Nabwire, as if he could divine the psychiatrist’s thoughts.1

Acanit was an exceptionally intelligent and well-educated woman, a banker. She had been born and raised in Kampala, Uganda, then immigrated to Edinburgh. In her twenties, she went to London for graduate school. She met and married her husband there, and they’d returned to Uganda in the mid-1990s because he was active in national politics.

She’d adapted well to the quieter life in this small town until two months ago, when she became convinced that a knife-wielding man was following her. She began complaining that people entered their home in her absence and stole objects as varied as her financial documents, the baby carriage, and family photographs she displayed on the walls. She even distrusted the people in her church congregation and her mother-in-law; she said they were plotting to harm her. She refused all visitors, even her family.

She heard things. She woke her husband late at night to listen to the unbearably loud clicks that she insisted were meant to keep her from sleeping. She also saw things and people who were not there, and about a month before the visit to Dr. Nabwire, she started hearing the voice of God telling her that she was “anointed with holy blood.” Around the same time, she began regarding her husband with suspicion. She said that she now recognized him as a servant of the devil, and she harassed him with prayers and loud warnings that their family could never be safe and complete if he did not repent.

The previous night he had come home to find her standing over their wailing daughter, shrieking Bible verses and looking at the child in a way that terrified him. Acanit insisted that she would never harm Dindi, but Felix decided to take an indefinite leave of absence from work so he could watch the child at all times, and he brought Acanit to his old friend Lutalo Nabwire, the psychiatrist at the HIV clinic.

Acanit was HIV positive, having contracted the virus in London from a former romantic partner. Felix was not positive and neither, fortunately, was Dindi; thanks to Acanit’s HAART regimen of the drugs Combivir, nevirapine, and abacavir, Dindi was born HIV negative, and Acanit did not suffer from opportunistic infections or other troublesome symptoms. Felix loved Acanit completely, but were he scrupulously honest with himself, he would have had to admit that he’d brought her to this modest HIV clinic rather than a large city hospital because he’d rather have her treated where he could rely upon Nabwire’s discretion; in Kampala, there was always the danger of a scandal to be politically exploited. Now he’d begun to regret this. Her symptoms surely had nothing to do with HIV, and she had no history of psychiatric problems or any other medical problems. Nabwire was an excellent doctor, Felix thought, but he should get Acanit to a hospital with more resources.

Nabwire began to assess her mental state, and at first Acanit was calm and fully oriented. She was aware of who she was, where she was, and what day it was, and she insisted several times, “But I feel well.”

After a few minutes of this, she seemed to yield to fear and anxiety and complained that she heard the clicking again. Soon, she began shaking and shouted, “God has anointed me with blood but the devil is interfering with me.” She burst into laughter for a minute, and then fell into a stony silence.

Nabwire took Acanit’s hand. “Why won’t you speak?” he pleaded. “I am trying to help you.”

Then he sat back, deep in thought. He believed he understood what was wrong; he had seen this before. As he weighed the words he would use to explain it to Felix, Acanit suddenly seized Dindi and began to shake her while shrieking about God and absolution of sin. It took both the doctor and her husband to rescue the terrified infant from her mother’s grip.

The nurse injected Acanit with a sedative while Nabwire explained, “Your wife is having a bad reaction to the medicine she is taking for her HIV, but don’t worry. It is completely reversible. We will keep her here for a while to treat her and find safer medicines for her. Afterwards she will be fine.”

“Do you promise?” Felix asked.

“Don’t worry; she should be as good as new with a change of medicine,” Nabwire assured him.

But privately Nabwire thought, Yes, she will recover, but only because you can afford the new medicines she will need. They are expensive and becoming more so as supplies dry up. Few of my patients are so fortunate.2

Acanit’s story illustrates a troubling and often overlooked phenomenon. For a long time, I thought it was in the nature of bacteria to be democratic, infecting hosts without regard to station. However, this is not always so, and indeed we have engineered sources of bias that result in very different disease prevalences from region to region.

Infections that cause mental disease are especially devastating for residents of developing countries, in part because tropical and subtropical climates harbor many poorly understood pathogens and poorly medicated infectious diseases but also because the health-care vacuum and the studied indifference of many drugmakers separate people of the developing world from preventive efforts and treatments. This allows infectious diseases like malaria, polio, rubella, and general paresis that have been tamed or conquered elsewhere to thrive there. Of the seventy billion dollars spent annually on medical research, approximately 10 percent is devoted to diseases that cause 90 percent of the global health burden, leaving one billion people affected by undertreated tropical diseases.

The scope of these problems is sweeping enough to merit its own book; vast swaths of the Indian subcontinent, poor regions of the Americas, and even poor Eastern Europe enclaves suffer in a similar health-care vacuum, but because of sub-Saharan Africa’s dramatic concentration of global disease, I will be focusing on examples from there to illustrate the issues.

Each year, up to three million deaths due to malaria and close to five billion episodes of clinical illness meriting antimalarial therapy occur throughout the world, with Africa carrying more than 90 percent of this burden. Dengue, leishmaniasis, African trypanosomiasis (sleeping sickness), tuberculosis, malaria, HIV disease, diarrheal illnesses, and helminthic (worm) infections constitute some the most deadly infectious diseases. Children are the prime victims, as these infections sap their vigor, retard their physical and mental development, and, in many cases, shorten their lives.

Medical drought

Devastated by colonial rape, the depletion of its rich natural resources, and the dismantling and neglect of its original health-care institutions, much of sub-Saharan Africa has been left to poor health and a ravaged medical infrastructure, and few physicians remain. A mere 750,000 health workers care for the continent’s 682 million people. The Organisation for Economic Co-operation and Development (OECD) estimates that this health-care force is as much as fifteen times smaller than in the thirty-four OECD countries that stimulate economic progress and world trade. Only 1.3 percent of the world’s health workers practice in sub-Saharan Africa, but the region harbors fully 25 percent of the world’s disease. This means that only one medical doctor practices in Africa for every one hundred in the United States, but the picture is even bleaker for psychiatric disorders: Nigeria, the continent’s most populous country, has only one psychiatrist for every two hundred in America.

Worse, already sparse psychoactive medications are disappearing altogether as pharmaceutical firms abandon their development in favor of lifestyle medications for conditions such as erectile dysfunction and gastrointestinal distress. Moreover, new psychiatric drugs are expensive to produce, unlike the “copycat” medications, which are minor tweaks of existing pharmaceuticals. Because copycat drugs are cheaper and easier to make, drugmakers focus on producing them instead of concentrating on needed drugs to address neglected medical conditions.3

A European College of Neuropsychopharmacology report warns that retrenchment in the flailing pharmaceutical industry places “research in new treatments for brain disorders under threat” as corporate behemoths such as Roche, Pfizer, AstraZeneca, and GlaxoSmithKline eliminate teams, cut funding, and shutter divisions dedicated to psychiatric drugs.4 The industry has been abandoning psychiatric medications since at least June 2011, when the British Journal of Clinical Pharmacology published an article entitled “Vanishing Clinical Psychopharmacology.” That same week, David Nutt, a neuropsychopharmacologist at Imperial College London, told reporters that “these are dark days for brain science.” At the 2011 meeting of the American Society for Clinical Pharmacology and Therapeutics, not one of the three hundred abstracts presented related to new psychopharmacological drugs.5

The wholesale abandonment of psychiatric drugs will be challenging enough for the affluent West, but it is disastrous for the undertreated people of the developing world, including vast swaths of Africa. This is because their access to these expensive medications is already woefully inadequate; any dearth will disproportionately affect the poor of the Global South.

In 2012, the journal Science Translational Medicine charged that the development of drugs for psychiatric disorders such as autism, schizophrenia, bipolar disorder, and depression has stalled as “major pharmaceutical companies recently announced substantial cutbacks or complete discontinuation of efforts to discover new drugs for psychiatric disorders.”6

Although India has long been a source of cheap medications for the developing world, its role has been hampered by vigorous patent protection under the World Trade Organization’s 1994 Trade-Related Aspects of Intellectual Property Rights, or TRIPS, statutes. A few developing nations, like Nigeria, manufacture many drugs, but 70 percent of them are generic, and the country engages in almost no new drug development.7

Western support is needed to supply psychiatric medication to the developing world. “Internationally, I believe the UN agencies like the WHO should be backing a global campaign,” said John Kufuor, Ghana’s former president and the special envoy for the Global Network for Neglected Tropical Diseases.8

In a perfect storm of psychiatric neglect, the dearth of psychiatrists and the scarcity of psychoactive medications has been joined by a wide-scale abandonment of antibiotic development. Profit-centered priorities of medical research have given us at least fourteen medications for erectile dysfunction but few new antibiotics and severely limited stores of the only fully effective medication against sleeping sickness, the most notable cause of infectious mental illness in Africa.9

“In recent years, the major pharmaceutical companies have been getting out of the antibacterial business,” writes Deborah Gouge10 as she explains that antibiotics are relatively unprofitable. Streptomycin and penicillin are seventy years old, which means they are off patent; this opens the door to generics and reduces prices. The short course of most antibiotics—less than two weeks—and the inevitable obsolescence caused by antibiotic resistance also limit profits. Of the thirty-six Western companies that made antibiotics in 1980, only seven remain.11

The lack of reliably available treatment for infectious diseases in the Global South will affect mental disorders directly, beginning with the challenges that deprived Africans of the only safe, effective medication against an epidemic killer and destroyer of minds. “When I think of infectious mental diseases,” says Laura Manuelidis, professor of neuropathology at Yale, “I think first of sleeping sickness.”

Sleeping sickness and mental havoc

As headlines blare news of AIDS, malaria, and Ebola, African sleeping sickness, or trypanosomiasis, seems to be forgotten, shrouded in silence. Yet sixty million West and Central Africans are at risk of contracting this parasitic disease, caused mostly by protozoa of the subspecies Trypanosoma brucei gambiense and transmitted by the tsetse fly. It resembles the familiar housefly, although the tsetse fly can grow to twice the common fly’s length, and a long, beaklike proboscis sprouts from its head. Its wings fold with such precision that it often appears to have only one wing. But the tsetse fly is no mere buzzing annoyance. It delivers a prolonged, painful bite that deposits the trypanosomes that seal its victim’s fate because they cause two regional forms of trypanosomiasis.

The disease is endemic to regions of sub-Saharan Africa and kills half of those it infects in the Central African regions of Uganda, the Democratic Republic of Congo, Sudan, Ethiopia, Malawi, and Tanzania.12 According to WHO, during epidemic periods in certain areas, “Sleeping sickness was the first or second greatest cause of mortality in those communities, ahead of even HIV/AIDS.”13

For months before their death, those stricken by African trypanosomiasis seem neither living nor dead, their zombie-like state brought about by the bite of the tsetse fly. The dying slip away exactly as they lived for the preceding year: silent, unmoving, and usually invisible. (A similar disease, American trypanosomiasis, or Chagas disease, threatens twenty-one South American countries, but it is caused by a different organism and requires different treatment.)14 But before T. brucei gambiense kills its victims, doctors say, it drives them mad.

The fly’s bite leaves a painful red chancre and is followed a few weeks later by the disease’s first stage, known as the hemolymphatic phase, wherein the parasites reproduce in the victim’s tissues, blood, and lymph fluid. The illness’s early symptoms—joint pain, bouts of fever, headache, and itching for a few days—seem innocuous and are often ignored or mistaken for malaria because they resemble those of the malarial fevers that are common in affected areas. The parasite has to be detected in a blood sample or in lymph or cerebrospinal fluid to establish the diagnosis, but health-care workers are rare in the affected sub-Saharan areas, and so the disease often progresses unnoticed.

The body unsuccessfully tries to fight off the infection, and after several months the second stage ensues. It’s known as the neurological phase, because the parasites, or trypanosomes, cross the blood-brain barrier to infect the central nervous system. The multiplying parasites cause the brain to swell, compressing blood vessels and evoking such dramatic mental signs and symptoms as behavioral changes, sensory disturbances, and a disruption of the circadian clock, coupled with confusion.15 These produce an irresistible daytime drowsiness that is followed by nighttime insomnia.

We tend not to think of trypanosomiasis as a mental disorder, but we should, because the term sleeping sickness describes only its best known behavior change; the others are far more troubling. Cathy Hewison, an Australian doctor who has worked for Doctors Without Borders’ sleeping sickness program in Sudan, explains, “It is an unpleasant and debilitating disease…. Symptoms include severe headaches and convulsions and people can become extremely aggressive and paranoid.” Because of their aggressiveness, her patients often are strapped to their beds. A Doctors Without Borders report entitled “Saving Lives in the Name of Vanity” showed why when it described how, in 2001, one of Hewison’s patients from Ibba village murdered his three-month-old niece while in a state of paranoid delusion. She adds that such events are not uncommon; a paranoid sleeping sickness patient once charged at her brandishing a plank he had torn from his bed because he thought she was trying to kill him.16

After six months to several years a victim may die,17 but the intensity and prevalence of infections vary from region to region and even from village to village, wreaking the worst damage on children. The parasite can also be transmitted to infants through breast milk.

Within the past decade, at least three regional outbreaks have swept through Africa. Fifty thousand to seventy thousand people were infected in 2005 alone, according to WHO data. This is a very broad range, but the absence of public-health infrastructures in most of the affected areas makes precise disease surveillance impossible.18

The first stage can be treated with pentamidine, which is relatively safe. Or doctors can use suramin, at the cost of serious side effects. But most toxic of all is the traditional second-stage treatment, melarsoprol. This compound of arsenic and ethylene glycol, the latter of which is better known to us as antifreeze, is as toxic as it sounds, killing one person in five. Moreover, once the patient falls into a coma, melarsoprol is worthless, since it cannot cross the blood-brain barrier. In previous years, there was no drug that could arrest the disease once coma set in, and the infected expired on mats in darkened rooms or in forgotten corners of their untended farms. Although sleeping sickness is usually a rural disease, some died forgotten in the streets of thronged Third World cities.19

For decades, doctors could treat sleeping-sickness patients only with cures that seemed as dangerous as the disease and that could not help them once they fell into the final stage of trypanosomiasis. But hope arose in 1970 when Albert Sjoerdsma, former chief of Experimental Therapeutics at the National Heart Institute in Bethesda, Maryland, discovered eflornithine (also known as DL-α-difluoromethylornithine, or DFMO).20

Merrell Dow acquired the patent and set about testing eflornithine as a treatment for cancer and various illnesses. But in 1987 an announcement that Dow’s new drug seemed to quell sleeping sickness threw long-standing economic tensions into sharp relief. In preliminary tests, eflornithine did more than simply relieve symptoms, like other sleeping-sickness medications; eflornithine seemed to be a true cure, killing the parasite by targeting an enzyme within it, ornithine decarboxylase.

The FDA approved eflornithine tests on human subjects in 1990, but the drug immediately hit a development roadblock: many pharmaceutical firms had a tacit prohibition against testing medications for use in tropical diseases, because those illnesses struck people without the means to pay high prices; there was no profit in it. Without such tests, the FDA would not approve the drug.

So instead, Merrell Dow continued to test eflornithine against cancer and other diseases for which a wealthy Western market existed. Fortunately, Simon Van Nieuwenhove, a Belgian physician working for the Belgian-Sudanese Sleeping Sickness Control Project, was able to obtain samples of eflornithine that he used on his own Sudanese patients.

The clinical tests showed eflornithine to be effective and safe, and it did indeed cure patients who had fallen into comas in the final stages of the disease, which no other medication had been able to do. Accordingly, researchers called it “the resurrection drug,” and it was rechristened Ornidyl for use against trypanosomiasis.

But very few sub-Saharan Africans with sleeping sickness could afford Ornidyl’s resurrection, and Aventis, which had acquired the patent, halted production in 1995,21 citing its low earning potential.22

The firm began seeking other, profitable, uses for its drug. One was found, and Ornidyl was quietly reborn as Vaniqa, a fifty-dollar-a-month topical treatment for women’s unwanted facial hair. Only after Doctors Without Borders discovered this and applied pressure to the drugmaker did it become available again for sleeping sickness, but not consistently so.

Let them take cake

As shocking as this withholding of medication from poor people of the developing world sounds, it is consonant with long-standing Western pharmaceutical policies. Of the 1,233 drugs licensed globally between 1975 and 1997, just four were devised to treat diseases of people in the tropics.23 Little has changed since then. The drug-development-and-distribution efforts of NGOs like the Gates Foundation have been very successful, but they can help only a minority of people at risk for just a small sampling of tropical disorders.

One chilling change is that the industry’s objections to providing medicines for non-Westerners are no longer tacit.

In 1996, Bernard Lemoine, director general of France’s national pharmaceutical industry association, countered pleas that essential medications be sold to the developing world at affordable prices by saying, “I don’t see why special effort should be demanded from the pharmaceutical industry. Nobody asks Renault to give cars to people who haven’t got one.” In January 2014, when India granted a compulsory license to ensure that Bayer’s $69,000-a-year cancer medication Nexavar would be sold at a price that Indians could afford, Bayer chief executive officer Marijn Dekkers angrily called the compulsory license “essentially theft,” insisting, “We did not develop this product for the Indian market, let’s be honest. We developed this product for Western patients who can afford this product, quite honestly.”

He is right that Indians cannot afford it, because the drug is priced at forty-one times the country’s annual per capita income.

Thanks to this recent dearth of antibiotics and other medications, treatments for the Third World infectious diseases that trigger madness remain rare, expensive, and fraught with their own risks. Although some pharmaceutical firms now partner with the Gates Foundation and other NGOs to supply affordable medications, an excellent development, this does not meet needs. December 2014 reports gave some heartening news of reinvestment in anti-infectives by firms such as Tetraphase Pharmaceuticals and Merck, but there remains the question of whether these patent-protected medications will be available to the poor residents of the developing world.

Fortunately, there are some other routes to disease avoidance. Prevention in the form of vaccines, access to clean food and water, and even mosquito nets to discourage the transmission of malaria sometimes provide safer, cheaper ways to avoid illness, but as discussed in chapter 6, prevention requires careful strategies.

The secret strife of worms

In its medical vacuum, the developing world is plagued by diseases that are unknown or underexplored, so we know less about the endemic infections there that may trigger mental disorders.

We do know that rubella, which has been largely banished in the United States by vaccines (though it has recently mounted a comeback), is rampant throughout much of the developing world. According to Robert Yolken of Johns Hopkins, the rubella virus is on the short list of those thought to trigger schizophrenia when acquired in the womb or by the young.

Then there is the seemingly ubiquitous malaria. When the Plasmodium falciparum strain of malaria24 attacks the brain, the result is cerebral malaria, characterized by progressive weakness, fever, coma, and brain swelling. It occurs in more than 575,000 people every year, most of them children younger than five living in sub-Saharan Africa. Without antimalarial treatment, it is always fatal, and even with treatment, it kills one in five of its victims. The survivors suffer a wide spectrum of neurological, behavioral, and mood disorders, from learning disabilities to blindness and epilepsy to behavioral changes so dramatic that they can be mistaken for schizophrenia.

This makes cerebral malaria a leading cause of childhood neurologic disability. Scientists still don’t understand how the parasite that causes malaria damages the brain. Some believe that it causes the red blood cells it infects to pack tightly in small blood vessels in the brain, blocking them and disrupting brain function, but other researchers think that the parasite damages the brain more indirectly, through inflammation.

Even a newly discovered type of infectious agent, the prion, has been proven responsible for mental illness in the developing world. Daniel Carleton Gajdusek observed kuru (not to be confused with koro,which is discussed in chapter 5) among the Fore people in the New Guinea Highlands. The Fore called kuru the “laughing sickness” for its distinguishing facial muscle spasm, which resembles a malevolent smile—the same risus sardonicus that is an ominous sign of tetanus. Gajdusek claimed that kuru was contracted and spread by women who practiced ritual religious cannibalism. The infectious agents attacked their brains, eroding them and leaving them full of holes, or “spongy,” hence the description of the disease as a spongiform encephalopathy. Gajdusek wrote that the kuru outbreaks stopped when cannibalism stopped, supporting his view that prions cause kuru. Robert Klitzman of Columbia and others confirmed Gajdusek’s claims, but some of his scientific contemporaries contested them. They pointed out that cannibalism had ended in the community as far back as the 1960s and that the decline of kuru was concomitant with health initiatives such as placing hospitals, clinics, and clean running water near the affected communities.

The team Stanley B. Prusiner led identified the infective, self-replicating proteins that Prusiner dubbed prions in an attempt to capture their proteinaceous and infectious character. Like the endogenous retroviruses discussed in chapter 2, which resemble both genes and viruses, these prions occupy a twilight zone between two entities: protein and virus.

Prusiner, director of the Institute for Neurodegenerative Diseases at the University of California at San Francisco, met opposition from many scientists and writers who doubted that proteins would act in this manner. Some characterized Prusiner as a media huckster and gave his prion theory no credence. But he all but silenced them when he won the Nobel Prize in Physiology or Medicine in 1997 for his work. There are still those who remain unconvinced of the existence of prions, and perhaps the most prominent and accomplished of these is Laura Manuelidis, head of neuropathology in the department of surgery at Yale. She has published papers offering evidence that Creutzfeldt-Jakob disease might be caused by viruses or other well-established agents of infectious disease.

She also thinks it likely that CJD is more common than other scientists have assumed and that it may be causing many illnesses currently diagnosed as Alzheimer’s.

Indeed, the case of George Balanchine, the Russian-born director of the New York City Ballet who is venerated as the father of American ballet, reminds us of how little we understand about CJD and its transmission.

Balanchine’s symptoms first appeared in 1978; he began frequently losing his balance and falling while dancing, which forced him to explain rather than demonstrate what he wanted from his dancers. He complained that music sounded distorted to him and that color was so difficult to perceive that he had to abandon designing his own sets. Balanchine’s balance, eyesight, and hearing gradually waned, and by 1982, he was incapacitated, as much by the mental confusion and memory loss he suffered as by the loss of control over his body. The man who had choreographed more than four hundred celebrated ballets “could not recall events that happened a few minutes before.”25

The doctors who diagnosed his CJD after his 1983 death do not know how or where he contracted it, but in his New York Times column on Balanchine’s diagnosis, Lawrence Altman mentions “a prominent neurosurgeon who had developed it, possibly from contact with a patient” and another patient who had developed Creutzfeldt-Jakob disease in 1974 after receiving a corneal transplant.26

In addition to familiar sources of infection like the plasmodia parasites that cause malaria and the unfamiliar prions behind kuru and CJD, there are many infectious agents of which we are unaware, especially in the health-care vacuum of the Third World, warns Robert Yolken of Johns Hopkins. He stresses that some of these unknown agents are likely to cause mental disorders.

However, physicians have long observed that even infestation with the familiar, ubiquitous worms and other parasites of the tropics can induce dire mental changes. Twenty years ago, J. Packman of Yale University wrote that “patients with parasitic loads are more likely to exhibit mental-status changes and there is an improvement in mental status of a subset of psychiatric patients following treatment for parasites.”27

These risks have been quantified in other countries. German researchers studied thirteen hundred people with trichinosis, a disease caused by a common parasite people can acquire from improperly handled or undercooked pork. The initial symptoms include abdominal discomfort, nausea, diarrhea, vomiting, fatigue, and fever, followed by a second phase of muscle aches, itching, chills, joint pains, and seizures two to eight weeks after ingesting the tainted food.

It can also cause mental symptoms, including delirium, accompanied by insomnia and central nervous system inflammation, or encephalitis, which the Germans found in nearly one in four of their subjects.

Diagnosing trichinosis requires sophisticated analyses with antibody assays that were developed in 2003, and such technology is rarely available in the Global South. Animals infected with trichinella are “most commonly found in pork in the United States and Europe,” according to the authors of Psychiatric Aspects of Infectious Disease Syndromes but this may not be so, because trichinosis may be dramatically underdiagnosed in the developing world.28

Neurocysticercosis is a common infection caused by a species of tapeworm in tropical countries. People in Latin America, Southeast Asia, and sub-Saharan Africa contract this from eating food contaminated with the eggs of the pork tapeworm Taenia solium, whose larvae accumulate in the victim’s muscles, skin, eyes, and central nervous system, where they trigger epileptic seizures. The larvae invade the brain directly and form cysts that can be clearly seen on CT scans. The lesions and swelling they cause are also visible. Sixty-five percent of infected people also display mental symptoms, from depression to psychosis. Moreover, neurocysticercosis is the most common preventable cause of epilepsy, because 80 percent of the fifty million epileptics in the world live in the Global South, often in areas where T. solium is endemic.29 Treatment requires years of the medications praziquantel and albendazole, which are not available in many affected areas. Fortunately, the preventive route can also help: handling and cooking pork properly and vaccinating the pigs that harbor the infection.

The disease was once rare in the United States, but it is rising in incidence due to immigration, and WHO calls it the food-borne parasite “of greatest global concern.” But control will be a challenge, in part because making a diagnosis requires a CT scan, which is rarely available in the affected poor rural areas.

It is harder to impute a mechanism to other infections whose signs are not visible, but the psychiatric literature is studded with documented associations between mental symptoms and parasites like giardia, roundworms, and Borrelia burgdorferi (the bacteria that causes Lyme disease), and these symptoms consistently vanish when the infection is routed, fulfilling one of Ian Lipkin’s proof requirements.

Yet despite the wealth of infectious agents in the developing world, the dearth of medical professionals who can diagnose, or even suspect, any resulting psychiatric illness ensures that the diseases—and treatments—remain well below the public-health radar.30

The physical ravages of AIDS are all too well known, from cancers and a universe of opportunistic infections to wasting and debilitating symptoms such as oral infections and intractable diarrhea. But HIV destroys mental health as well. Few diseases wreak as much psychological havoc as undertreated HIV disease. The virus sabotages the central nervous system and brain, while the opportunistic infections it permits demonstrate the terrible versatility with which HIV promotes mental illness.

HIV is the most deadly infectious disease in human history. Thirty-five million people are infected, and seven of every ten of them live in sub-Saharan Africa. A UNAIDS report revealed that more than half of all people with HIV do not know they are infected, thanks in large part to the paucity of medical care in most of the developing world. In the West, the disease is largely controlled because people who are tested and learn their HIV status can benefit from effective treatment with highly active antiretroviral drug therapy, or HAART, sometimes referred to as active antiretroviral drug therapy, or ART.31

But in the developing world, such treatment is harder to come by. By late 2013, 11.7 million people in low-and middle-income countries were receiving ART, but according to WHO figures, this still leaves 22 million untreated people. This means that three of every five people in the Global South suffer from untreated HIV infection.32 Fortunately, most—67 percent—pregnant women living with HIV in poorer countries do receive ART, which can prevent the transmission of HIV to their unborn children.

We know that people with HIV are more likely than uninfected people to suffer psychosis and commit suicide. Ninety percent of the people with HIV who experience psychosis fall prey to delusions that they are being persecuted or even that others are transmitting thoughts into their minds. Hallucinations (usually hearing voices) and confusion also occur. But they may also be subject to emotional states that veer from profound depression to irritation to euphoria. Experts estimate that as many as 40 percent of U.S. residents living with HIV suffer from anxiety disorders.33

However, experts still disagree on just how the virus drives mental illness. The psychosocial stress of having a chronic disease that impairs health, requires constant monitoring, and carries a social stigma certainly increases the risk of anxiety and other mental symptoms, but researchers believe that the virus itself also causes dementia and psychosis in approximately 15 percent of people with HIV.34 The virus causes psychosis by various means, some of which interact.

AIDS dementia complex, or ADC,35 leads to cognitive decline and lessens the ability to focus, think, concentrate, and problem solve.

A 2013 report in the German Journal of Psychiatry analyzed forty-seven studies of HIV and psychiatric disturbances published from 1970 to January 2012.36 The authors found that the direct effects of the virus on the central nervous system could produce cancers and organic brain syndromes that included dementia and psychosis. To give just one example, the virus encourages free calcium to flood the spaces between cells, and calcium levels drive neurotransmitter release, so the finely coordinated firing of synapses in the brain becomes wildly inappropriate, disrupting interneuron communication and affecting a wide variety of brain functions.37

Such brain dysfunction usually appears in late-stage HIV infection, typically after the disease has progressed to full-blown AIDS, but most affected patients are still in their thirties. The mental disturbances, like the mechanisms HIV uses to assail the mind, are legion—paranoid delusions, hallucinations, cognitive impairment that prevents logical thought, memory loss. Less frequently, HIV causes catatonia resembling that suffered by survivors of the 1918 epidemic of encephalitis lethargica, or sleeping sickness, who were treated by Oliver Sacks as described in Awakenings.

But other factors also spur patients’ mental derangement—opportunistic infections, the failure of a weakened immune system to fight off attacks on the brain by other pathogens like the tuberculosis bacterium or the T. gondiiparasite, and the substance-abuse disorders found in disproportionate numbers of people with HIV. The German study also unveiled a terrible synergy in the ravages of HIV on mental health. People with HIV who develop psychosis suffer greater neurological impairment, and so do those who have a history of drug abuse. The infected with histories of drug abuse are also likely to fare more poorly and die earlier than other people with HIV and AIDS, leading the authors to conclude, “The high co-prevalence suggests a possible [causal] association between HIV infection and psychosis.”38

The variety of HIV-related psychoses are treated by conventional antipsychotics, but fortunately, most people don’t need them for long; the psychotic symptoms tend to abate as their physical disease is brought under control. This is a good thing, because even the medications used to treat HIV can contribute to dementia and psychosis. For example, up to half of those who take efavirenz as part of their drug therapy experience vivid dreams, nightmares, insomnia, and mood symptoms. These mild disturbances seem far outweighed by the medication’s benefits, but others suffer more significant psychiatric problems, including mania, depression, suicidal thoughts, psychosis, and hallucinations.

Genetics also plays a role. Cytochrome P-450 is a major enzyme involved in drug metabolism, and those people with a particular variant of the gene that codes for it are more likely to respond to efavirenz with psychosis. This is an important risk factor for Ugandans as well as for Western Europeans; doctors should monitor patients on efavirenz closely, but this is less likely to happen in the developing world, where just getting HAART to HIV-positive people is a challenge.39

Hazards of modernity

In order to reduce HIV infections and other diseases, the UN mandates antenatal care in a health facility as part of the Millennium Development Goal (MDG), and various well-intentioned campaigns urge mothers-to-be to give birth in hospitals. Yet recent discoveries belie the assumption that giving birth at a hospital is always the best way for Africans to avoid infection.40

In the representative African countries of Kenya, Tanzania, and Zambia, wealthier, employed, better-educated, urban-dwelling women are more, not less, likely to be infected with HIV. These are also the women who are most likely to give birth in a hospital. Part of the problem, as I discussed in a 2007 New York Times editorial, is the spread of HIV by well-meaning health-care workers struggling to give quality care under deplorable conditions that often preclude effective infection control.

Meticulous sterile technique is needed to prevent the spread of HIV, trypanosomiasis, and other diseases that can imperil mental health. But in poor undeveloped countries, safe devices are as scarce as doctors. Despite an unsupported assumption that the AIDS crisis in Africa is mostly fueled by patient carelessness and sexual promiscuity, reused SUDs (single-use devices) and unsterilized needles help to spread infectious illnesses throughout Africa with terrible efficiency. POZ blogger Simon Collery wrote,

It is not known what proportion of HIV transmission is a result of sexual intercourse and what proportion is a result of other modes of transmission, such as exposure to contaminated medical instruments, unsafe cosmetic or traditional practices…. The assumption that most transmission is a result of sex is a prejudice, rather than an empirical finding. The assumption that transmission through various non-sexual routes is low is a result of not looking for evidence that would demonstrate such transmission and ignoring any evidence that comes to light, which it usually does inadvertently.41

But the evidence for iatrogenic, or healer-caused, infection does exist, although it is often greeted by denial. As recently as 2007, the World Health Organization maintained that the reuse of syringes without sterilization accounts for 2.5 percent of new HIV infections in Africa, but a 2003 study by David Gisselquist in the International Journal of STD and AIDS found that up to 40 percent of HIV infections in Africa had been caused by contaminated needles used during medical treatment.42 Even the conservative WHO estimate translates to hundreds of thousands of infections.

Infections that are more common in the West than in the Global South drive mental-disease rates too, beginning with influenza. Americans think of the flu as an ailment of temperate Western climes, but influenza struck one of every five hospitalized African respiratory patients between 2006 and 2010, and one of every ten outpatients. It drives significant morbidity and mortality in Africa,43 and in fact, Africans suffer more complications than Western patients. Elderly South Africans with influenza, for example, are four times more likely to die than their U.S. counterparts.44 Administering vaccines to prevent influenza would greatly reduce the related risk of acquired schizophrenia, especially in newborns and the young, as detailed in chapter 2. Similarly, vaccines against the GAS infections that cause PANDAS, as established in chapter 3, could ward off anorexia, Tourette’s, and OCD.

Medicines with borders

There is as yet no preventive against T. gondii, nor a vaccine against the hepatitis C virus, which goes hand in hand with depression; up to seven of every ten people with hepatitis C suffer from depression.45Nor is there a preventive for the sleeping sickness that breeds paranoia and murderous aggression.

But even if these vaccines and antibacterials existed, they would probably not benefit people of the Global South. Vaccines against influenza and antibiotics for GAS infections do exist, but they are hard to come by in the developing world. How hard? No one seems to know; a 2014 survey report of thirty-one African countries concluded that “influenza vaccines and antiviral drugs are available in many countries in Africa but coverage estimates are low and remain largely unknown.”

When available, they are prohibitively expensive. When they are affordable, they are sometimes shunned by the people who desperately need them. The medically damaging injection practices and, especially, the use of ethically suspect research have fomented a loss of trust in vaccines in Nigeria. Much of the news coverage focuses on the contention by suspicious Africans that Western vaccines spread HIV and cause sterility.46 These fears may seem unfounded to some, but they are based on a well-documented contemporary history of harms at the hand of white and Western-trained physicians.

In March 2000, Werner Bezwoda, a cancer researcher at South Africa’s Witwatersrand University, was fired after conducting medical experiments involving giving very high doses of chemotherapy to black breast-cancer patients without obtaining informed consent. Dr. Michael Swango was ultimately convicted of murder after pleading guilty to killing three American patients with lethal injections of potassium, but he is also suspected in the deaths of sixty others, mostly in Zimbabwe and Zambia during the 1980s and ’90s. In 1995, Richard McGown, a Scottish anesthesiologist practicing in Zimbabwe, was accused of five murders and convicted in the deaths of two infant patients whom he had injected with lethal doses of morphine. Wouter Basson, the former head of Project Coast, South Africa’s chemical and biological weapons unit under apartheid, was charged with killing hundreds of black citizens of South Africa and Namibia from 1979 to 1987, many via injected poisons. He was tried but not convicted by an apartheid-holdover judge in a South African court, even though his lieutenants testified in detail and with consistency about the medical crimes they conducted against blacks. Malicious research agendas, such as the Project Coast division that vowed to create agents to selectively harm or sterilize black Africans in the guise of vaccines, are well documented. In 2015, the South African medical association censured Basson for the killings that took place under his direction during apartheid.47

Moreover, the widely publicized CIA perversion of vaccination programs as fronts for covert operations such as the search for Osama bin Laden and other political schemes has done much to feed Third World distrust of Westerners proffering injections. At least one CIA sham vaccination program encouraged the spread of infection by providing only one injection of a three-dose protocol, an inadequate treatment that made people believe they were protected against disease when they in fact were not.48

The practical result of all these reckless mistreatments is unambiguous: suspicious patients avoid care, and this iatrophobia, or fear of physicians, means that “conquered” diseases such as polio are seeing a resurgence on the African continent.49 Even when vaccinations are delivered by the most dedicated health-care workers, poverty makes treatment in the developing world fraught with risk.50 Infection control to prevent the spread of disease is difficult or impossible when there is limited access to clean water and no access to the antiseptics and cleaning agents that we take for granted in the West.

Given these varied challenges, what would be the smart move to protect the developing world from infectious diseases that may destroy minds, from the ailments spread by worms and tsetse flies to HIV and influenza?

Obviously, affordable antibiotics and psychoactive drugs must be made available. Clean water and the construction of toilets can do much to eliminate sources of infection and to damp virulence, as it denies microbes easy access to hosts. But simpler, cheaper pharmaceutical approaches could also play a role, including drugs like aspirin,51 which protects the brain via its anti-inflammatory effects, suggests Michael Berk of Australia’s Deakin University School of Medicine: “Aspirin can reduce oxidative stress and protect against oxidative damage. Early evidence suggests there are beneficial effects of aspirin in preclinical and clinical studies in mood disorders and schizophrenia.” Moreover, Berk notes, “Epidemiological data suggest that high-dose aspirin… one of the oldest agents in medicine, is a potential new therapy for a range of neuropsychiatric disorders.”52

In neglected lands teeming with untamed infectious threats and unaddressed disease, there is much room for improvement utilizing both classic public-health measures and sophisticated infectious-disease strategies of the sort analyzed in chapter 6.

But it is a mistake to think that when Westerners address these threats to physical and mental health, we are helicoptering in just to save the bodies and minds of the downtrodden. All our medical fates are inextricably linked, and by treating disease abroad, we help to save ourselves.



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