Hydroxychloroquine in Brazil: A Virtual Research Adventure

Linda Rabben
©2020

This was supposed to be a quiet summer, staying at home, washing hands, keeping a safe distance and wearing a mask outside. But instead I found myself doing virtual research about the Brazilian government’s ill-conceived Covid-19 policies and their disastrous effects on the country’s indigenous communities.

For almost 30 years I worked on and in Brazil, starting with pre-doctoral ethnographic fieldwork in the late 1970s. I traveled to Brazil to do research 18 times between 1978 and 2005, working for nongovernmental organizations and as an independent scholar, publishing four books on Brazilian human rights issues. I’ve followed or worked on Brazilian issues only sporadically since 2014, but I do keep in touch with Brazil colleagues.

This story started on June 14, 2020, when a colleague emailed a message about members of an urban indigenous community in Manaus. Hospitalized with Covid-19 symptoms, they “found themselves unwitting participants in a clinical experiment to receive hydroxychloroquine as a treatment.”  The words “unwitting” and “experiment” started alarm bells ringing.     

I remembered the provision in the International Covenant on Civil and Political Rights (1966): “No one shall be subjected without his free consent to medical or scientific experimentation.” It seemed unlikely that those indigenous patients had given their informed consent to receive hydroxychloroquine (HCQ) in a clinical trial while hospitalized with Covid-19. Was the Brazilian government committing a major human-rights violation or even genocide by giving a drug that might be both dangerous and ineffective to indigenous people without obtaining their informed consent?

I immediately thought I should try to convince human rights or indigenous advocacy organizations to denounce Brazilian human rights violations during the pandemic to international bodies such as the Inter-American Commission on Human Rights and the International Labor Organization. But I needed evidence to do that. Sitting at home in Takoma Park, Maryland, how was I going to find it?

Meanwhile the Covid-19 epidemic was exploding in Brazil, resulting in the second highest national total of coronavirus cases in the world. Brazil’s president, Jair Bolsonaro, was trying to minimize the importance of the disease and was touting HCQ as a miracle drug to prevent and treat the virus. By the time I found out about the indigenous deaths in Manaus, Bolsonaro had already fired two health ministers who didn’t want to approve the drug and had appointed an army general to the post. Plans to distribute HCQ or chloroquine to indigenous communities moved ahead.

Recent clinical trials and other research on chloroquine and HCQ in many countries have tended to discredit these drugs as unsafe and ineffective preventatives or treatments for Covid-19. For example:

“Study finds no benefit, higher death rate in patients taking hydroxychloroquine for Covid-19”[1] (April 21, 2020)

“Hydroxychloroquine fails to help hospitalized coronavirus patients in US funded study” (May 7, 2020)[2]

“FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems” (June 15,2020)[3]

“Hydroxychloroquine studies show drug is not effective for early treatment of mild covid-19” (July 16, 2020)[4]

Since I don’t do research in Brazil anymore, I’ve lost most of my contacts there. But I sent emails about HCQ to Brazilian journalists, medical researchers, public health experts, human rights organizations and anthropologists; most did not reply. I had to ask other colleagues closer to home for help. Some sent me news reports about the dire situation of indigenous people and the administration of HCQ to vulnerable populations in Brazil. Others gave me email addresses of their contacts in the country. 

Laura R. Graham, an anthropologist who has worked with the A’uwẽ-Xavante people for decades, wanted to know more about HCQ. She and Edson Krenak, a Brazilian indigenous anthropologist, were preparing an open letter to Brazil’s president under the auspices of the American Anthropological Association. At their urging the Society for the Anthropology of Lowland South America and Cultural Survival already had denounced the Brazilian government’s failure to protect the health, lives and livelihoods of indigenous peoples during the pandemic.[5]

I was able to contribute information about HCQ to the AAA letter, which went to Bolsonaro in early July. It is now posted in English and Portuguese on the AAA website.[6]

Then I suggested to Laura Graham and Edson Krenak that we work together on an op-ed about the plight of Brazil’s indigenous people during the pandemic. We spent more than a week on the op-ed; the AAA’s press officer helped us edit it and submit it to online publications. After decades of trying without much success to publish articles about Brazil in US periodicals, I am disappointed but not surprised that the op-ed has not yet found an outlet.

In mid-June someone sent me a press release from the US State Department.

Joint Statement From the United States and Brazil Regarding Health Cooperation

Office of the Press Secretary
FOR IMMEDIATE RELEASE
[May 31, 2020] 

The American and Brazilian people stand in solidarity in the fight against the coronavirus. Today, as a demonstration of that solidarity, we are announcing the United States Government has delivered two million doses of hydroxychloroquine (HCQ) to the people of Brazil. . . .

Further, in continuation of the two countries’ longstanding collaboration on health issues, we are also announcing a joint United States-Brazilian research effort that will include randomized controlled clinical trials.  These trials will help further evaluate the safety and efficacy of HCQ for both prophylaxis and the early treatment of the coronavirus.

Going forward, the United States and Brazil will remain in close coordination in the shared fight against the coronavirus pandemic and the ongoing regional response to safeguard public health, further limit the spread of the coronavirus, advance the early development of a vaccine, and save lives.[7]

 The press release came out soon after a delegation of Brazilian officials visited the White House. (Several of them tested positive for Covid-19 on their return home.) The announcement raised ominous questions in my mind: Was the US government colluding in the Brazilian government’s human rights violations by supplying HCQ and collaborating on clinical trials of a drug that already had been shown to be unsafe and ineffective? Would the trials be conducted in accordance with national and international law?

In late June I tried to get answers from the State Department to many questions raised by the press release. The Brazil desk officer, who was working from home, refused to talk to me; he said he’d been instructed to refer all inquiries about Brazil to the press office. Repeated attempts to reach the press office by email and phone were fruitless. (A phone message left at the Brazilian Embassy also went unanswered.)

Twice State Department press officers replied to my email request for information about HCQ in Brazil by sending me names of several people who could answer my questions. The department’s phone operator could find none of them in the directory. When I phoned the press office, a recorded message said that no messages were being taken at that extension. Finally, on my fourth or fifth attempt to speak to the press office, the main operator told me that the State Department was “closed down,” and nobody there was taking calls.

As a human rights worker I had received help with several Brazilian cases from my US senators. For example, during the US government shutdown of 1997, a senator’s two-sentence fax to the US Embassy in Rio de Janeiro had helped a community activist who had received death threats to obtain an emergency US visa for himself, his wife and his child. 

This time I thought my senators might like to know that the State Department was closed. Unsurprised, a Senate staffer told me she would try to get answers to my 14 questions about the press release from her contacts at the State Department. After a week she reported that she had had the same experience I had. She asked if the senator could send my questions in an official letter to the State Department. Their personnel are required by law to respond to such senatorial inquiries. But, she warned, it could take up to a month to get answers. Was I in a hurry?

I contemplated the hundreds or thousands of indigenous people in Brazil who were dying of Covid-19 or of HCQ’s collateral effects. Of course I was in a hurry. But my colleagues and I had gathered enough information to finish our carefully phrased op-ed, in which the words “allegedly” and “reportedly” would substitute for confirmed facts.

At the same time I decided to contact medical researchers about informed consent. Having done most of my research as an independent scholar, I knew very little about university and government requirements for the conduct of research on human subjects. A helpful colleague at the University of Maryland’s Human Research Protection Program sent me a link to the International Clinical Trials Registry, which turned out to be an important source of information.

In the registry I found detailed descriptions of three clinical trials of HCQ in Brazil.

RBR-3cbs3w [Hospital Alemao Osvaldo Cruz, Sao Paulo] [Co-sponsor: WHO]

Randomized, pragmatic, double-blind, placebo-controlled clinical study, evaluation of Hydroxychloroquine for prevention of hospitalizations and respiratory complications in outpatients with confirmed or probable diagnosis of COVID-19

Registration Date: April 2, 2020, 8:11 p.m. Last Update: June 2, 2020, 8:06 p.m. 

RBR-9d8z6m [Hospital do Coracao, Sao Paulo]

Open and controlled trial of hydroxychloroquine and azytromicyn use to prevent complications in patients infected by new coronavirus (COVID-19): a randomized controlled trial

Registration Date: March 24, 2020, 10:09 a.m. Last Update: May 28, 2020, 1:23 p.m. 

RBR-95yjmq [Hospital Santa Paula, Sao Paulo]

Randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of hydroxychloroquine and azithromycin versus placebo in the negative viral load of participants with flu syndrome caused by SARS-CoV2 and who have no indication for hospitalization

Registration Date: April 27, 2020, 11:57 a.m. Last Update: April 29, 2020, 11:38 a.m.[8]

Only one of the three trials, at the Hospital Santa Paula, mentioned informed consent as a requirement for participation in the trial. The detailed description of the study at the Hospital Alemão Osvaldo Cruz—one of dozens of HCQ “Solidarity” trials that the World Health Organization was sponsoring around the world—didn’t mention informed consent.

None of the directors of the three trials responded to my emailed questions about informed consent. Later the WHO announced that it would stop some, but not all, of the HCQ Solidarity trials, because the drug was ineffective when administered with certain other drugs.

The chief of the Adult Clinical Studies section of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine answered some of my questions about informed consent. He described the great care he and his researchers take when they carry out clinical trials with very poor people in remote parts of developing countries. He couldn’t explain why two of the three São Paulo trials didn’t mention informed consent.

Jair Bolsonaro announced in early July that he had tested positive for Covid-19 and popped a pill he identified as HCQ in his mouth at a press conference. “I feel perfectly well,” he said. 

Meanwhile, Edson Krenak, who is studying abroad but keeps in touch with friends, relatives and indigenous health workers in Brazil, sought answers to my questions. He heard that one of the 11 patients who died in the Manaus clinical trial was an elderly indigenous man. Another informant reported that government health workers were handing out chloroquine tablets to indigenous patients as if they were placebos, then sending the Indians back to their villages with no follow-up. His sources were anonymous, however, and I couldn’t confirm their information. 

I realized that a reporter or investigator would have to do research on the ground to obtain information from indigenous Covid survivors, health workers and others with firsthand knowledge of the situation.

It is difficult to determine how many Covid-19 patients in Manaus and other cities are indigenous. The Brazilian government classifies Indians as indigenous only if they live in villages or reserves in rural areas. Once they move to the cities, as thousands have, they are no longer eligible to receive medical care from the special indigenous health service, SESAI. 

Indigenous people are often excluded from scientific studies because language difficulties or cultural differences could make it impossible for them to give informed consent. Some clinical trial participants might have been indigenous and should have been excluded from the trial. But if they were classified as “white,” they might have been included. 

In early July I read about a Brazilian military medical team that took 13,500 doses of chloroquine to the huge Yanomami indigenous territory in far-northern Brazil. An independent news agency reported, “The operation is intended to counter criticisms that the Bolsonaro government does not do enough to protect indigenous people from the epidemic.” [9]

Before entering the reserve (without the required permission from the Indians), military team members took a Covid-19 test known for its frequent false-negative results in asymptomatic or pre-symptomatic people. They gave out chloroquine in several villages but left the territory after a week—not enough time to follow up. In light of the long history of unauthorized and catastrophic experiments on indigenous people, it is difficult to call this incursion well-conceived or beneficial.

A Brazilian colleague sent me government documents, including protocols for HCQ administration to indigenous people. The recommended dosages were about as high as those in the ill-fated Manaus clinical trial. I found this document especially disturbing, partly because of its banality. Giving such high doses of HCQ to indigenous patients with preexisting conditions could kill them.

Science magazine published a long article about the Manaus trial in its June 22 issue. It described the well-intentioned mistakes that might have led to the deaths of 11 out of 81 participants and the political, professional and personal consequences of the trial. The researchers received death threats from Bolsonaro supporters, who accused them of deliberately overdosing the patients in a nefarious effort to discredit the president and his favorite cure-all. 

The article concluded: “‘It’s a nightmare,’ [the study director] told Science in a video call. For weeks he hasn’t been able to stop worrying that ‘my whole career is gone’ or agonizing over the death threats against his family. ‘The day someone tells in your social media, that they’re going to kill your children to make you suffer the way you made other people suffer, you will understand what I’ve been through,’ he says.” [10]

What caused the deaths of the 11 participants? Covid-19 or complications resulting from high doses of HCQ? This is one of many questions I can’t answer from 5,000 miles away. I’ve managed to collect a handful of reports of indigenous people who died of heart attacks after receiving HCQ as a treatment for Covid-19. But those accounts are anecdotal—worthless to a medical researcher. A friend asked if the victims of the experiment in Manaus would have been autopsied. I doubt it. Rushing thousands of plague victims into mass graves probably leaves no time for postmortems. I can only hope that a fieldworker will set out to uncover the truth. 

Brazilians themselves have tried to draw attention to the government’s lethal malfeasance during the pandemic. The National Confederation of Health Workers asked a Brazilian Supreme Court justice in early July to stop the production, supply and prescription of hydroxychloroquine and chloroquine for Brazilian Covid-19 patients. The health workers claimed that government support for the drugs “contradicts scientific, technical and sanitation guidelines of national and international authorities.”[11]

Even more significantly, on July 26 a coalition of Brazilian health workers’ unions went to the International Criminal Court to denounce genocide and crimes against humanity committed by the Brazilian government against minority groups, including Indians, during the pandemic. I hope that international human rights organizations will join this effort.

After a very long month of research, I believe—but still can’t prove—that the Brazilian government has deliberately or negligently harmed indigenous and other vulnerable populations during the pandemic. I also believe that the US government has enabled these serious human rights violations by sending HCQ to the Brazilian government. 

Despite my inability to prove my contentions, I have learned a great deal from this exercise in remote research. I can now discuss questions such as: How is medical research conducted? What are the ethics of clinical trials? How are the prevention and treatment of disease politicized? How can patients’ human rights be protected during large-scale medical emergencies? 

The most challenging questions remain: What should you and I do with this information? “After such knowledge, what forgiveness,” if we do nothing?

July 28, 2020

Linda Rabben is an associate research professor of Anthropology at the University of Maryland and the author of Brazil’s Indians and the Onslaught of Civilization and other books on human rights.

[1] https://www.cnn.com/2020/04/21/health/hydroxychloroquine-veterans-study/index.html

[2] https://www.cnbc.com/2020/05/07/hydroxychloroquine-fails-to-help-hospitalized-coronavirus-patients-in-us-government-funded-study.html

[3] https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-chloroquine-and

[4] https://www.washingtonpost.com/health/2020/07/16/hydroxychloroquine-studies-show-drug-is-not-effective-early-treatment-mild-covid-19/

[5] https://www.salsa-tipiti.org/covid-19/salsa-letter-to-brazilian-authorities/; https://www.culturalsurvival.org/news/open-letter-jair-bolsonaro-brazil-failing-protect-health-indigenous-peoples-during-covid19

[6] https://www.americananthro.org/ParticipateAndAdvocate/AdvocacyDetail.aspx?ItemNumber=25775

[7] https://br.usembassy.gov/joint-statement-from-the-united-states-of-america-and-the-federative-republic-of-brazil-regarding-health-cooperation/

[8] http://www.ensaiosclinicos.gov.br/rg/RBR-3cbs3w/; www.ensaiosclinicos.gov.br/rg/RBR-9d8z6m/; www.ensaiosclinicos.gov.br/rg/RBR-95yjmq/

[9] https://www.roraima1.com.br/ 2020/07/01/militares-distribuem-cloroquina-para-indigenas-de-roraima-em-acao-contra-coronavirus/

[10] www.sciencemag.org/news/2020/06/it-s-nightmare-how-brazilian-scientists-became-ensnared-chloroquine-politics

[11] www.correiobraziliense.com.br/app/noticia/politica/2020/07/02/ interna_politica,868907/celso-de-mello-da-5-dias-para-pazuello-explicar-uso-da-cloroquina.shtml)