Bio-control for Mosquitoes: Opportunities Lost

James Northup

    I am going to relate to you a sad story; one that involves a bright promise of hope for the future, only to be dashed by shortsighted and destructive human tendencies.

Early Promise, but then Civil War.  The story starts in the 1970’s with the discovery of a new biological control agent for mosquitoes, Romanomermis culicivorax, first isolated in Louisiana and developed at the USDA Diseases Effecting Man Labs in Gainesville. By 1979 the results of field trials of this control against the mosquito vectors in a malarious region of El Salvador had been so dramatic that it led to an unprecedented two-part publication in Science Magazine, December of 1979 and January 1980. The project had reduced the Anopheles albimanus population by 95%, but the civil war in El Salvador closed down the project and the Salvadorans were bereft of hope for relief from the scourge of malaria.

Enter the University of California, but Alas, a New Civil War.  Fortunately for the world, the UC system, the crown jewel in the world for research in the biological control of mosquito vectors, and the mosquito abatement districts of California kept bio-control alive and prospering, husbanding research and production of Gambusia affinis and Romanomermis culicivorax. The work here at UCD brought worldwide acclaim to UC for the pioneering research into the mosquito-pathogenic fungus, Lagenidium giganteum. And in 1983, responding to the desperate appeal of the Health Ministry of Colombia, UCD equipped a collaborative project with mosquito sampling materials while the Sutter-Yuba Mosquito Abatement District furnished one hundred million eggs of Romanomermis to be utilized in an isolated region of Choco Province, Colombia. Once again a 95% reduction of Anopheles albimanus was achieved, only this time the human epidemic was monitored for two years and showed a reduction in the prevalence of the disease from 23% to near zero. This reduced rate persisted for nearly two years on a single inundative release. In June of 1985 the Revolutionary Armed Forces of Colombia shelled the laboratory and the project ground to a screeching halt. Once again civil war destroyed a promising start!

What Civil War in California?  Now, here in California we face the encroachment of a new mosquito-borne disease into our ecosystem, the West Nile Virus, and I wonder what civil war has taken out the production of Romanomermis or Lagenidium here where it was developed? And while that question may not have an obvious answer, the shortsighted despairing consequences of regressing to the crop-duster mentality of pest control are obvious. 

Enter the Plague?  When the SYMVCD District Manager was queried in the Davis City Council chamber about possible unintended effects on flea populations from the aerial spray program he replied there would not be any, due to the nighttime schedule of the spray. This is a non sequitur. Fleas, the vectors of bubonic plague, as nest parasites, are most commonly present in lawns and turfs frequented by dogs and cats. The larval stage is always in the nest, while the blood-feeding adults hop on and off the host for feeding. They most certainly will become exposed to a widespread broadcast of insecticides from the air. And while the District Manager claims there is no indiscriminate use of toxics, the distribution of pyrethrum and piperonyl butoxide from aircraft is the epitome of indiscriminate application since it cannot selectively target what it touches. The widespread broadcast of low concentrations of materials in this fashion is the recipe for creating resistance in non-target insects. Plague is chronically present in rodent populations in areas of California such as Lassen County and even Golden Gate Park. If resistance is induced in the flea populations, there will be no effective control available when antibiotic resistant plague encroaches upon the California ecosystem. We will then truly understand what a major urban epidemic of insect-vectored disease is really like!

Weighty Responsibilities.  It is my belief that drastic measures introducing toxics into our environment must be restricted to critical epidemic emergencies and we must assure ourselves of the availability of the less-dangerous toxins such as pyrethrum so that they will be effective if needed. There must also always be scientifically established risk analyses to determine when such protocols should be initiated. And, most importantly, the benefit of the treatment must be established with scientific certainty.

Major Exaggerations.  The risk of West Nile Virus has been greatly exaggerated by the spray proponents. Amazingly, after a year of promulgating the claim of grave risk from WNV, when the District Manager was asked on July 25 to stipulate specifically the worst infection rates yet seen for WNV and to compare them to malaria or yellow fever, the reasons that vector control was created in the first place, he could not cite the numbers for any of the three mosquito borne diseases. For public clarification, the highest rate of infection cited in the literature to date was in Ontario Province, Canada, with a rate of 1000 symptomatic infections per million. In California, where the climate and mosquito populations are different, the highest rates of infection, spray or no spray, are less than 500 per million. This was in very rural Glenn County. Urban Los Angeles County experienced an occurrence of 40 per million without aerial spray in 2004, and in the second passage in 2005 without aerial spray it was 6 per million. Sacramento’s occurrence with an aerial spray program was approximately 150 per million.

Let’s Get Real.  To put this in perspective, in all the years WNV has been present in the USA there have been a total of 762 fatalities. In any one year in the last decade California has had more than 8,000 fatalities from influenza.  Here in California more than 400 times as many people died of influenza last year than from WNV. A physician would have a difficult time recommending a vaccine for WNV, if one were to be developed, because the risk of adverse reaction to the standard pharmaceutically prepared vaccine is greater than the risk of exposure to serious disease from WNV. In fact, the natural vaccination from the mosquitoes may be less risky than any future pharmaceutical vaccine. And, of course, the comparison the District Manager was unable to make for us, yellow fever and malaria can end up infecting more than half the population in major urban epidemics. They were once both prevalent in regions of North America, but development of water management and sewer systems, adequate shelter for most people, public health delivery systems and the introduction of mosquito abatement at the beginning of the last century have removed these scourges from our radar. We are at a distinct risk for malaria epidemics here in rice country, and such serious epidemic possibilities should be the concern of vector control, not WNV.

No Respect for Science?  Our most vigorous complaint about the spray program is the failure to present the public a thorough and scientific assessment of either the risks or benefits of this program. The dictum has been, as reiterated at the Council Meeting, that since the solution is very dilute it can’t be harmful, or “the dosage makes the poison”. This seems an incomplete assessment on the part of a scientist, since the real dictum is “the susceptibility makes the poison and determines the dosage”. The papers that proponents of this view have been circulating have been uniformly deficient in one important aspect. Only one portion of one publication has dealt with the aerial distribution of insecticide, and that was malathion and not the pyrethrum formula used by SYMVCD. Only one actually deals with inhalation exposure, and though it has an elegant experimental design it cannot extrapolate to assessing the risk from aerial distribution.

Flawed Studies.  All of these studies have the common flaw of failing to consider a number of risk issues.  First, they postulate the perfect performance of the spray apparatus at distributing uniformly-sized droplets with uniform concentrations of insecticidal materials. There is no consideration given to the possibility of failure in the agitator, nozzle or computer controlled spectroscopic sensors. Any combination of failures in these components could lead to the distribution of highly concentrated pyrethrum or piperonyl butoxide. No assessment is made concerning the probabilities of such events in spray operations, though they surely do occur.
    However, even given the techno chauvinism of such an assumption about perfect performance of human artifacts, there is a great error in assuming the droplets will maintain uniformity in size, concentration or spatial distribution once released. The certainty is that air movement created by the aircraft itself will disrupt the “perfect” distribution. Some droplets will collide and aggregate. There will be differential evaporation due to the differing size of the aggregating versus dispersing droplets leading to differing concentrations of pyrethrum. The smaller concentrated droplets will have the opportunity to collide and aggregate leading to larger, more concentrated droplets. In short the material distributed from the airplane will vary greatly in dosage by the time it reaches the ground.

Major Problems for At-Risk Groups.  All these studies also fail to consider the special susceptibilities of at-risk groups in the population. Both pyrethrum and piperonyl butoxide are toxic to a wide range of organisms to differing degrees. Both poisons are toxic to healthy people at the dosage of between 750 mg to 1 gram per kilogram. But the liver toxicity and neurotoxicity of pyrethrum as well as the liver toxicity of piperonyl butoxide are significantly greater in persons with liver disease since the enzymes from the liver are what detoxify the poison in healthy persons. All infants under six months age are more acutely susceptible since they do not produce the full complement of liver enzymes. Effects that are delineated as sub-acute in healthy persons will be potentially fatal to those suffering from neurological diseases such as Parkinson’s disease or MS.  Those who suffer asthma or COPD (Chronic Obstructive Pulmonary Disease, or emphysema) will be seriously at risk to the inhalation exposure and for this specific reason many areas of the country, such as Washington DC and Bethesda  around the NIH, opted not to spray at all out of concern for those suffering from asthma.  The “inert” ingredients, which are the preponderance of the non-aqueous formula, are equally a concern for asthmatics.

Risk, Yes.  Effectiveness, No.  All the risk considerations aside, the most damning failure on the part of SYMVCD is around the proof of efficacy of the spray. None of the risks can be justified if the treatment isn’t curative, and it isn’t. Though Vector Control claims a drop in the mosquito counts consequent to the spray and a decline in the virus prevalence in the mosquitoes, this simple citation is misleading. In the aerial spraying of Sacramento last summer, the mosquito counts dropped in the weekly sample after the spray because the wind was blowing too strongly for crop dusters or mosquitoes to fly. As soon as the air stilled the counts showed an increase 70% higher than before the spray, i.e. trap 2100G went from 140 Culex to 246 Culex between Aug.7 and Aug 28. This increase is nearly 3% per day. A UCD lab has generated life-table data on rice-field mosquitoes showing a 4% daily growth rate for an undisturbed population during the month of August when they hit their peak. This would imply at best a 1% impact on the growth of free-living mosquito population from the spray. The appearance of declining frequencies in the pooled virus sample is an artifact of that same exponential population growth. All newly emerged adults are free of virus and only those on the order of five days or older can have acquired it and transmitted it. Unless the sample pools are segregated for age, the frequency of virus observed in the samples will appear to be declining at the same rate that the population is increasing.  A constant rate of infection would appear to be a 4% decline in an undisturbed population.

The Numbers Don’t Add Up.  The other claim to efficacy comes from a table from the California Department of Health Services.  On examining the table the only conclusion that can be drawn is the author or editors failed to check the sums before publication. This table, which colorfully exhibits the enumeration of symptomatic WNV cases in two-week segments for four areas of Sacramento County as well as the rest of California, fails to correspond accurately between the listed totals and the sum of elements. While the total for Sacramento is listed as 154, the four regions listed for Sacramento County sum to only 110. The actual distribution of these missing 44 cases in the table may or may not change the conclusions drawn, but in their absence, no valid conclusion can be drawn. The recent assertion that many of these 44 were cases without a known onset date is patently specious since they come from the sample pool that had a known onset date. The assertion that there were cases without a known residence make me wonder why the residence wasn’t tracked down, at least to follow up on the health of the patients. The assertion that there were more regions to Sacramento other than sprayed and not sprayed listed in the table makes me wonder why there wasn’t another row in the table to include the complete count of symptomatic cases with known onset date. The data of the timeline of infections by itself is valuable and really had to be included for this “study” to be scientifically credible.

Bogus Assumptions, Methods.  In examining corroboration for this table from the Health Services web page private citizens cannot discover where the errors occur, since the location of cases is listed by county only, not by residential address. However, even if the missing cases were discovered to be distributed only in “control” regions, the assumption that persons contracted their infections exclusively in their places of residence is patently absurd.  This kind of assumption might be accurately applied to diseases vectored by lice or bedbugs, but even in those cases a good epidemiologist would employ some landscape epidemiology to rule out certain endemic foci such as sleazy motels, etc. The other great problem besides this failure to measure the location of transmission is the failure to measure the infection rate in a scientific way. To date no serological assays have been performed to determine the actual extent of the infection rate. The Third World study in Colombia was able to perform such tests in a nearly inaccessible terrain. The California Health Services certainly could do the same in urban Sacramento.

    Contrary to the assumptions implicit in the state experts analysis, the majority of infections of WNV were probably contracted exterior to the domicile at some outdoor activity in a sylvan setting. The District Manager did concur with this assessment of location of transmission when asked at the Council meeting. The best research on the ecology of this disease so far, published by William Reisen, delineates the virus’ passage into and through southern California in 2003 and implies the amplification of the virus is occurring principally in rural settings and the vector seems to be Culex tarsalis.  This contradicts the assumption of principally domiciliar or even urban transmission for this disease. Without this assumption that all transmission was in or near the home this analysis can’t prove anything about the relationship between the spray and transmission of the virus even when they correct the arithmetic.

We’ll Scare Those Little Critters to Death.  What can be seen in the Health Services “line list” is that the peak expression of symptomatic cases for Sacramento County was 15 new cases on August 1. This number was declining to 8 new cases on Aug. 6 and 7 and by August 8, the day the spray began, this number had declined to 4 new cases or a two-thirds decline in advance of the aerial spray program. Since the virus has an incubation of 3-14 days prior to expression of symptoms, the first possible reduction in symptomatic cases due to aerial spray couldn’t have occurred until Aug. 11. Apparently the Health Services believe that the threat to utilize aircraft frightened the mosquitoes into surrender prior to the spray!

    Viewing the data for Riverside County, where no such threat was made, should dispel this belief. It, too, had multiple cases in June had the peak expression of symptomatic cases on Aug 1 and had more than 60% of infections before Aug 10. The pattern of the infection rates through time in the two counties is very similar though Riverside had no massive aerial spray campaign. Riverside had less than half the rate of infection as Sacramento. Adjacent Yolo County also had less than half the rate of infection without the benefit of the aerial spray.

Safe and Effective Alternatives.  Meanwhile, the Sac-Yolo Vector Control is not utilizing the full compliment of safe and effective biological control agents. No mention is given to their efficacy as alternatives to this aerial spray protocol, so we will introduce these comparisons. The mosquito-parasitic nematode, Romanomermis culicivorax, has been shown to reduce mosquito populations by as much as 95% on inundative releases. The mosquito-pathogenic fungus, Lagenidium giganteum, has exhibited similar efficacy and is even more specifically effective against the putative vectors of WNV. Both these agents will establish ongoing populations and remain effective at controlling mosquito populations over a number of years. Both these organisms are obligate parasites of larval Culicidae, mosquitoes, and infect nothing else. That is, they present no risk to either human health or the environment.

    Unfortunately, neither of these agents can be cultured artificially in a way that retains their infectivity. For this reason they are not being produced commercially. However, Sac-Yolo used to culture its own Romanomermis in vivo, but there has been no mention of re-establishing such a culture program or developing one for Lagenidium.  With the expertise of the Vector Control District such programs should be easily devised. Such a mass culture facility could also produce Bacillus spaericus and Bacillus thuringiensis ser.H14 both of which have efficacy in reducing mosquito populations. Such a facility would be a valuable resource to all of California since this renewable resource could provide the seed culture for many similar programs around the state.

A Slam-Dunk Risk-Benefit.  It seems almost ridiculous for the District to consider multiple millions of dollars in expenditures on insecticidal agents and not spend a dime on these safe and effective biological agents. The risk-benefit comparisons should be obvious. On the one hand we have a material with dubious efficacy and a guaranteed universal exposure to an incompletely assessed risk; and on the other we have a proven safe and effective set of biological controls.

Keep Our Tax Dollars Here.  When cost questions are introduced the comparison is even more exaggerated. The added labor required to culture the District’s own biological alternatives would end up both a benefit to community employment and substantially less costly for the District’s budget than procuring poisons and aircraft delivery systems. That the District is choosing ongoing outlays for a 100% depreciable investment in distributing poison as opposed to investing in a permanent facility for production of a renewable resource is beyond any reasonable comprehension.