JOHN BOOSS, MD
DEPARTMENT OF VETERANS AFFAIRS
NATIONAL DIRECTOR OF NEUROLOGY AT
VA CONNECTICUT HEALTHCARE SYSTEM,
WEST HAVEN, CT
SUBCOMMITTEE ON BENEFITS
HOUSE COMMITTEE ON VETERANS' AFFAIRS
July 16, 1998
Thank you Mr. Chairman and members of the Subcommittee on Benefits for this opportunity to discuss the matter of potential long-term neuropsychological outcomes associated with malaria and in particular, cerebral malaria. My name is John Booss and I am the Director of Neurology for the Department of Veterans Affairs based at VA Connecticut Healthcare System in West Haven, Connecticut, and Professor of Neurology and Laboratory Medicine at the Yale University School of Medicine. I am testifying before you today as one of the Department of Veterans Affairs experts on neurological conditions and their potential association with the combat experience. I am one of thousands of clinician/researchers in the VA system who provide clinical care for veterans and who conduct research relevant to some of the unique health problems, combat-related and non-combat-related, posed by participation in military service. The issue that we are discussing today is complex and controversial and is an example of why VA supports clinician/researchers.
VA has long been concerned about infectious diseases and their outcomes among veteran populations. Our research programs in infectious disease range from endemic infectious agents (such as malaria) in areas to which service members have been deployed, to emerging pathogens (such as multiple drug resistant TB) that pose new threats and concerns about the health of the veteran community.
The Office of Research and Development Medical Research Service reviewed a research proposal from Dr. Nils Varney from the Iowa City VA Medical Center in 1988 to carry out research on the neuropsychiatric consequences of cerebral malaria in Vietnam veterans. Following a competitive merit review process, funds were awarded to Dr. Varney for his proposed research from 1989 - 1992. A paper titled "Neuropsychiatric Sequelae of Cerebral Malaria in Vietnam Veterans" reporting on this research was published in 1997 in the Journal of Nervous and Mental Disease (185:695-703). Much of the controversy surrounding this report involve four issues:
This is not to say, however, that Dr. Varney’s hypothesis lacks value. Indeed, further investigation could refine our understanding of the long-term consequences of malaria infection. What we suggest is that an assessment of Dr. Varney’s work reveals some methodological and interpretational problems, that should be carefully considered before we make decisions that change health benefits policy. We must look at Dr. Varney’s work in the larger context of our scientific knowledge about malaria.
Before I go on to discuss Dr. Varney’s work in more detail, I want to consider some background regarding malaria itself. Malaria is caused by infection of the human with a parasite of the genus Plasmodium. The diagnosis of malaria is made by examination of blood smears for the parasite. Humans are infected with Plasmodium through inoculation by the Anopheles mosquito carrying the organism, which it received by biting an infected human. There are several species of Plasmodium, one of which is Plasmodium falciparum. Infection with Plasmodium falciparum leads to falciparum malaria, and is the cause of "cerebral malaria". Of all falciparum malaria cases, many published studies have estimated that approximately 2% are diagnosable as "cerebral malaria" which causes loss of consciousness and other neurological, psychological, and neuropsychological signs and symptoms. One study in particular examined 1,200 cases of falciparum malaria among troops deployed to Vietnam and found 19 who fit criteria for cerebral malaria. The paper reporting these findings was published in the Journal of the American Medical Association in 1967 (JAMA, 202:679-682).
With this background, I will now turn to Dr. Varney’s work.
An earlier study of malaria from Dr. Varney’s group was reported in VA Practitioner in February 1989. In that paper, 30 Vietnam veterans were studied who reported having had malaria, accompanied by at least 12 hours of amnesia. Twelve of 17 medical records supported a diagnosis of malaria, but the remainder were reported as lost or destroyed. There was no report of examination of blood smears for the malarial parasite, nor was the diagnosis of "cerebral malaria" reported from the available medical documents. Hence in the 1989 report the diagnoses of cerebral malaria were not established medically. All subjects had co-existing medical conditions that could have contributed to the reported findings. Hence there is ambiguity about the cause of the neuropsychologic findings reported.
Unfortunately, the report of Dr. Varney and his group in the November 1997 issue of The Journal of Nervous and Mental Disease does not resolve the ambiguities. There is again no requirement for laboratory verification of the "malaria group". Of 40 veterans studied, service records were found for 37, of which 14 had a diagnosis of malaria cited. A search for the diagnosis of cerebral malaria was not reported, and no report of blood smears for the parasite was made. This is in contrast to medical reports on malaria at the time of the conflict in Vietnam in which microbiologic confirmation of actual infection was obtained [JAMA, 202:679-682, 1967; Military Medicine, 138:795-802, 1973]. To reiterate, the most recent report from Dr. Varney’s study did not require medical diagnosis of malaria in order for a subject to be included in the malaria group, nor did inclusion require a medical record citation of cerebral malaria. This is a significantly lower diagnostic standard than the wartime reports.
Other researchers have examined the long-term effects of malaria infection on brain function. In 1998 Anthony Dugbartey and colleagues reported in the Journal of Nervous and Mental Disease (186:183-186, 1998) on their follow-up study of 142 individuals in Ghana with medically documented uncomplicated falciparum malaria (i.e. not cerebral malaria). They evaluated these individuals’ psychiatric and cognitive status using self-report questionnaires and compared their results with a similar group of 30 individuals with no life-history of malaria. These researchers found comparisons between the malaria and control groups showed small differences on scales of anxiety and depression with no observed differences in higher level brain functions such as thinking clearly or remembering. They suggest that falciparim malaria may cause a long-term, subclinical or subtle mixed depression-anxiety syndrome.
Dr. Varney’s paper presents certain issues as factual that diminish the validity of his conclusions. First, he states that "it is estimated that about 250,000 Vietnam veterans were hospitalized for falciparum malaria during the course of the war." The basis for that estimate is unclear, as the reference for this figure cited by Dr. Varney (Connor, et.al., 1976) does not contain that figure. A compilation of military cases from another source (Clinical Infectious Diseases, 16:320-329, 1993) is considerably lower. He further states that "those who were hospitalized were at high risk for cerebral malaria." This latter statement is true only if one accepts a rate of 2% among all falciparum malaria cases as constituting a high risk.
To summarize, whether the 40 veterans studied by Dr. Varney ever had cerebral malaria has not been medically demonstrated and the extrapolation of the number of veterans with cerebral malaria appears to be in error. Evidence from other researchers indicates that uncomplicated falciparum malaria results in, at worst, mild psychiatric sequelae. What about veterans who actually had cerebral malaria in Vietnam? Could they have neuropsychological effects to this day? I don’t think we have a conclusive answer to that question, but given the serious acute nature of cerebral malaria, the possibility certainly exists. Were a veteran with a history of falciparim malaria with or without documented acute cerebral symptoms to complain of symptoms suggesting complex partial seizures, anxiety, and/or depression, careful clinical evaluation of those symptoms and appropriate therapy would be warranted. This would constitute accepted practices and standard of care in any VA hospital.
The Department of Veterans Affairs is particularly mindful of the disease burden, both combat and non-combat, carried by those who have served in deployments around the world. Research such as Dr. Varney’s, despite our reservations, reminds us that diseases are complex. For this and other reasons, the Department of Veterans Affairs will continue to fund scientifically sound research that explores disease associations that might affect the health of our veteran patients, either acutely or in the long term.
Thank you Mr. Chairman. I will be happy to take any questions you may have.