Claim of Possible Drug-Resistant Malaria in Angola Withdrawn

A paper reporting a possible case of drug-resistant malaria in Angola appeared last July (reported here), meeting with scathing incredulity and direct calls for retraction from the World Health Organization and some members of the malaria research community.

The surprising firefight appears to have been concluded, not with retraction but the publication of letters from the authors of the original paper and its detractors at WHO and Mahidol University. The paper’s authors now acknowledge that “our report of a Vietnamese worker returning from Angola with severe Plasmodium falciparum malaria not responsive to artemisinins is unlikely to indicate that artemisinin resistance has reached Angola.”

The paper and letters appeared in Emerging Infectious Diseases, published by the Centers for Disease Control (CDC).

Critics point out that the delayed clearance time seen in the case was nearly ten times slower than that seen in drug-resistant malaria in Southeast Asia, the only region in the world with clinically-verified resistance to artemisinin-based anti-malarials. Genetic testing after the publication of the paper did not find any of the mutations in the K13 gene associated with resistance. Also, the drug used in the case came from a batch that was withdrawn because of quality issues.

In rebuttal, the authors of the original paper note that the drug used, while substandard was far from lacking any activity. The paper is not being withdrawn and the case is not closed, say the authors: “the reasons for the lack of response to artemisinins in this patient remain unknown and are under continued investigation.”

WHO also says it is still looking into the same geographic area of Angola from which the disputed case originated.

Olivo Miotto, who previously predicted the paper would be retracted, said more recently “it was a mess-up, as was suspected at the time by those more interested in science than fiction.”

According to Annette Erhart, one of the paper’s authors, the Vietnamese investigators knew that publishing the case would expose them “to criticisms about the way the patient was managed.” The group published nonetheless because “for the first time, they were confronted to a situation where AS [artesunate] did not work at the dosage recommended by the national guidelines.” Continued Erhart: “The attitude of the WHO is discouraging anybody to report suspected resistance cases, while it should be actually the opposite.”

WHO’s Pascal Ringwald, contacted last September about the case, said “Globally it is amazing how journalists misunderstand artemisinin resistance and they do not investigate on what should be investigated.” Although the paper had been published by the CDC and elicited public statements of concern from prominent malaria researchers, Ringwald insisted on his own knowledge: “I do not know which is or are your sources but I think that you do not trust me.” The case, he said, "is absolutely not interesting and not important.” Ringwald forbade all further inquiries: “In the future please use your other sources of info and do not contact me for any kind of reason.”

A ceasefire of sorts appears to have been brokered. Said Miotto: “I think everyone is just letting it drop—not worth any arguments.” Patrick Kachur, chief of malaria at the CDC, declined to answer questions about the matter directly, referring inquiries to the CDC press office. Kachur did allow that “I was hoping these [letters] would be ready to share a lot sooner.”