This week in Malaria World, MMV (Medicines for Malaria Venture), a Swiss based NGO founded with funding from Rockefeller foundation and others, announced clinical trials of MMV371, an ester-linked acetyl derivative of atovaquone, one of the components of GSKs Malarone, a combination of atovaquone and proguanil that is taken orally.

Drugs.com report side effects for atovaquone/proguanil; severe or uncontrolled vomiting or diarrhoea; fever, mouth sores; problems with speech, balance, or walking; severe skin rash; nausea, stomach pain, loss of appetite, dark urine, clay-coloured stools, jaundice (yellowing of the skin or eyes); easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin.

Just imagine how much worse side-effects could be when directly injected.

The trial itself, in conjunction with Quotient Sciences, is taking place in Nottinghamshire, UK and it is unclear what will be given to the placebo group. The first cohort will receive 112 mg or placebo by intramuscular injections. Second and third cohorts to receive double of quadruple doses, up to 446 mg. I wonder will the placebo be a true placebo? I reported that the trial of R21 vaccine used a relatively toxic Indian polio vaccine instead of a true placebo.

More information on MMV371 development is available in Malaria Journal article by El Gaaloul et al.

Can we compare trial subjects in Nottinghamshire, UK to the likely target patients, perhaps malnourished children under five? Pending positive outcomes of the study, clinical trials in malaria-endemic countries are expected to begin in 2026. The promotors claim the final product could have the potential to complement existing interventions such as vaccines; seasonal malaria chemoprevention (SMC), mainly administered to children under five. I have more discussion of SMC drugs in my book ‘Malaria is Spread by Mosquitos?’ and previous blog posts.

I was pleasantly surprised to note that the lead article in malaria world this week is an article by the editor of Malaria World Journal, Bart Knols, expressing concern about the impact of chemicals used for mosquito control. In the article entitled ‘A shot in the foot: Could chemical control of malaria vectors threaten food security?’, Knols expresses concern that the malaria research community has become enslaved to thinking that controlling malaria mosquitos equals the use of chemical insecticides.

The article does include the unsupported statement ‘Although chemical control has undoubtedly saved millions of lives, which, morally speaking would immediately justify its continued use, it has many sides that may ultimately cost more lives than it saves.’ There is no reference to support the life saving claim of insecticide use, so this article is clearly a long way from questioning the overall transmission story. But at least it is a useful start that such an eminent researcher in the malaria community is willing to question some of the dogma.

Knols states in his article, that after a posting on LinkedIn arguing against aerial spraying of insecticides in Africa, he was called a tree-hugger!

However, Knols still wants to kill mosquitos and is a believer in the mosquito transmission story. Much of his article is promoting other methods of killing mosquitos such as traps or genetic methods. He admits he is actively involved in the development of insecticide-free products and strategies for mosquito control. He has links to a company, K&S Holding BV, that has developed mass trapping options for dengue vectors based on the use of Biogents A.G. (Germany) traps.

Nonetheless, if members of the malaria research community are starting to become aware that poisoning the environment might have negative consequences, perhaps soon some of them, less financially reliant on the purveyors of poison to kill mosquitos or ‘treat’ people, might start to look more deeply for the real causes of the deadly ailment called malaria.

(Picture from mosquitojoe.com)

Three articles this week reminded me how unquestioned the belief that malaria is spread by insect vectors is. This belief is supported by confirmation bias. Every result that suggests a connection is highlighted. Any evidence that does not support the belief is explained away or ignored. This is no different than the approach of Ross or Grassi >120 years ago.

First, in the climate sceptic website wattsupwiththat there was an article entitled ‘European Trainee Doctors to Have Fake Malaria Climate Myths Added to Their Studies’. It challenges the climate change scare that higher global temperatures will increase malaria by increasing mosquito habitats, pointing out that malaria, then know as ague was well known in England during the cold Little Ice Age. I could point out, that while present, Anopheles mosquitos are rare in England and were likely rarer in colder times. The article blames an uptick in malaria cases in USA and Europe on travellers coming from countries where Malaria is present. I commented with a reference to usmalaria.com and only received negative responses such as ‘…but given the weight of historical evidence that controlling mosquitoes reduces Malaria transmission…’ from the author Eric Worrall who does not seem to understand that correlation does not prove causation. And this is a website, most of whose readers have open minds to examine Climate Change. But not mosquito transmission of malaria.

Second, in news-medical.net an article called ‘Surge in malaria cases linked to aircraft-transported mosquitoes’. The 145 cases described from nine countries, most in France, Belgium, and Germany, were classified as airport malaria, luggage malaria, or both, and quaintly called Odyssean Malaria. Half resided or worked near or at an international airport. Half of the cases were people born in Africa. There is no evidence presented that these people were bitten by a transported mosquito and it is unclear how often this happens. It only serves to prove that if physicians have reason to suspect malaria based on belief in ‘Odysseus the Mosquito’, they are likely to test for plasmodia. Otherwise, they wouldn’t, and you won’t find what you don’t seek.

Third, in Malaria World this week an article titled ‘Why does malaria transmission continue at high levels despite universal vector control? Quantifying persistent malaria transmission by Anopheles funestus in Western Province, Zambia’ by Ashton et al. (Maybe the two are not connected? ) The detailed study, which used good scientific methods, calculated that Children not sleeping under insecticide-treated nets (ITNs) experienced 13.6 bites per person per six-month season, while ITN users received 1.3 bites per person. They conclude that one infectious bite per person per six-month transmission season, must be sufficient to maintain high malaria transmission and burden.

Many believe because they have no reason to examine the issue, like me prior to 2022 prophylaxis decision. And others because their livelihood depends on it. To increase awareness I am making pdfs of my books available free of charge.

(Image from https://www.sciencejournalforkids.org/articles/should-you-worry-about-mosquitoes-on-planes/)

In Malaria World this week there is reference to a study purported to support an increase in the dosage of Primaquine to children with Plasmodium vivax malaria. However, is that the main conclusion that can be taken from the study?

The study, ‘Primaquine for uncomplicated Plasmodium vivax malaria in children younger than 15 years: a systematic review and individual patient data meta-analysis’ by Commons et al published in Lancet Child and Adolescent Health, made two major observations from the 27 studies considered eligible for analysis, the majority of which were carried out in the Asia-Pacific region.

1) Dosing with primaquine and especially higher doses reduced the likelihood of detecting Plasmodia is the blood up to 180 days later. Their analysis suggested that increasing the total dose of primaquine from 3·5 mg/kg to 7 mg/kg would reduce the risk of recurrent Plasmodium vivax parasitaemia by more than 40% in all children and by about 60% in children younger than 5 years.

2) Compared with no primaquine, children treated with any dose of primaquine had a greater risk of serious adverse events and gastrointestinal symptoms on days 5–7 after treatment (those receiving highest dose 146% more likely than no primaquine). And, interestingly, data on adverse events and serious adverse events were only available from six (22%) of the 27 studies.

There is no detail in this meta-analysis of the testing that was carried out for Plasmodia in the included studies. I expect they were mostly RDT results. There is no indication that any of those in whom Plasmodia were detected were otherwise unwell. However, it is quite clear that those who suffered severe side effects of the drug were unwell.

Is this type of study useful discovering what aids health, or a means to justify dispensing of more pharmaceuticals? The study was organised by WorldWide Antimalarial Resistance Network (WWARN) and the authors are funded by Australian National Health and Medical Research Council (NHMRC), the Wellcome Trust, US National Institutes of Health and the US President’s Malaria Initiative (CDC), the Malaysian Ministry of Health, Medicines for Malaria Venture and Bill & Melinda Gates Foundation.

There were three articles this week in Malaria World related to Ghana. Two articles related to vaccination programmes. A retrospective assessment of a pilot RTS,S rollout in in 2019-2021 (Adjei et al) did not even attempt to examine if the vaccine actually worked at preventing the target disease. It just examined its administration.

And despite there being no evidence that the vaccine has a benefit, another article publicises WHO and UNICEF’s plan to roll out the RTS,S/AS01 malaria vaccine to an additional 200,000 children annually in Ghana.

The third article is a study of the illness using RDT testing, the SD Bioline Malaria Ag Pf (05FK50), to detect plasmodia in children and provides interesting data. Dosoo et al carried out a community‑based cross‑sectional survey of the prevalence and factors associated with malaria among children aged 6 months to 10 years in the Greater Accra Region of Ghana.

The study was extensive. It included 17,033 children (8,741 aged 6–59 months and 8,292 aged 5–10 years) from 8,305 households. It considered age, gender, location – urban, semi-rural or rural, use of insecticide treated nets, material of house construction – walls, floors and roofs, type of windows, use of screens on windows, source of water and whether the house had electricity.

The overall prevalence of plasmodia was low (4.1%) which is a level consistent with other studies for Ghana. But this low level makes statistical certainty of any hypothesis difficult to disentangle from confounding factors. Nonetheless, interesting observations are possible.

In their univariate analysis the authors found age of the child, location of residence, presence of net in windows of the house, main source of drinking water (open water source), presence of electricity and materials used for walls, floor and roof of the house were associated with malaria positivity while ITN use, gender and type of window were not.

At least one observation is counter-intuitive, the higher occurrence in older (5-10 years) children 4.9% vs 3.3% for children aged 6–59 months. Another very interesting observation was identical occurrences (4.1%) whether the participants used insecticide treated nets (ITN) or not.

Overall the factors that suggested higher occurrences of malaria plasmodia are factors that suggest poverty. Houses with mud walls had 11.3% positivity compared to 2.7% for painted cement or brick walls. Wood or rudiment floors had ~8% compared to 1.2% for ceramic tiles. Grass roofs 15.9% compared to 1.8% for tiled roofs. Houses without window screens had 12.1% compared to (3-4%) for houses with. Houses using open water sources, 10.8% compared to 3-4% for closed or bottled water sources. The few houses without electricity had 7.7% positivity.

Children living in poverty are more likely to have markers of poor health. Experience in Europe and North America showed that when communities become better off malaria disappeared. And the negative result for ITNs strongly suggests occurrence of malaria has nothing to do with mosquitos.

An article referenced in Malaria World this week is A historical perspective of malaria policy and control in India by Sam et al. India is important in the history of the medical establishment malaria transmission narrative because it was where Ronald Ross, the British Army medic who supposedly demonstrated the mosquito plasmodium connection, carried out his research. His research mostly examined other germs, Proteosoma and Halteridium, in birds and Culex mosquitos (not Anopheles). Even at his time his work was downplayed by Grassi and others (see my translation of Grassi’s Studi di uno zoologa sulla malaria). However, the award of the 1902 Nobel prize cemented Ross’ place as the man who found out how malaria is transmitted.

Sam et al, in their historical perspective, sponsored by the Bill and Melinda Gates foundation, point out that when India gained independence in 1947 there were ~75 million cases of malaria and 0.8 million deaths annually. As a result of a campaign using DDT the number of cases reduced to <50,000 and deaths to zero by 1961! But mosquitos, especially Anopheles culicifacies (the most important vector of the nine Anopheles species in India), developed resistance to chlorinated insecticides. So, malathion was introduced instead for internal residual spraying. In the 1980s treatment with Sulfa-pyrimethamine and in the 2000s artesunate plus sulfadoxine-pyrimethamine was added to the programme. All in all, much like the establishment approach everywhere else. Poisoning the environment and prescribing drugs!

Current annual cases in India are reported in the article at fewer than 200,000 and deaths are ~100. In a country the size of India (1.5 billion), is a disease that caused no deaths in 1961 and fewer than 100 now worth attention? Malaria is an illness with non-specific symptoms diagnosed by the presence of microbes in the blood that clean up damaged tissue. If you don’t look for these microbes, you won’t find it. This is why there are no cases in countries supposedly free of malaria (unless the medics look for them because the person recently returned from a malaria country).

The evidence does not suggest there is a major problem with malaria in India.

In Malaria World this week there is a link to a communication by epidemiologist, Prof. Fred Binka, who urges the Ghana government to prioritise investment in malaria research. He is advocating for investment in new tools and technologies that could cut down on the reproduction and transmission of mosquito, the vector, he claims, spreads malaria. He despairs that the Ghanaian government will not financially support studies, he recommended, that could focus on trapping mosquitoes before mating. He said “within country, virtually nothing.  Most of the work that people are doing, the research money, comes from outside the country.”

Binka is credited in the article as the principal investigator during the Mosquito Bednet Studies, which found that sleeping under an insecticide-treated net significantly helped to reduce malaria (transmitted by anopheles mosquito) mortality and morbidity (Binka et al, 1996). This is what has resulted in the use of insecticide treated net as a major primary health care policy and tool in malaria control and prevention in Ghana.

But is this research convincing? The study was large. In 1993 insecticide treated bednets were distributed to 6053 compounds for the test group and the control group who did not receive nets was of similar size. There was a 17% reduction in all-cause mortality in children aged 6 months to 4 years. The reduction in mortality was confined to children aged 2 years or younger, and was greater in July-December, during the wet season and immediately afterwards.

But when there are such obviously different test and control groups, one that receives nets and one that does not, can we be sure that there weren’t other unnoticed interventions that benefitted the group who were visited by the researchers dispensing the nets?

Follow up studies did not show benefits. A follow up study by Binka and coworkers Mortality in a seven-and-a-half-year follow-up of a trial of insecticide-treated mosquito nets in Ghana, made the much more modest claim that they found no indication in any age group of increased mortality in the ITN group after the end of the randomized intervention! The article is behind a paywall so I can’t dig deeper. Another study by Browne, Maude, and Binka in 2001 found no benefit in reduction of plasmodia by distributing treated bed nets to pregnant women.

Nonetheless, Binka calls on his probably cash-strapped government to pay for exotic mosquito control research.

For my research on Malaria is spread by mosquitos? I was impressed by the work carried out by Ghanaian naturopathic doctor, Emmanuel Kwame Asenso. He attributes the cause of malaria not to plasmodium spread by mosquitos, but rather to filth in the liver. Dr Asenso published a 48-page book titled The Natural Steps for Curing Malaria – Malaria is Filth in the Liver, as reported by Aheng (2014).

Asenso believes the only treatment plan way to permanently eliminate malaria from one’s life is through detoxification of the liver. He also believed that good nutrition, that is the consumption of vegetables, herbs and greens and clean lifestyles, were primary means of building a strong immune system to ward off diseases. The main ingredients used in the systemic detoxification are hot pepper, coconut oil and lemon, measured and given to a patient proportionately with his or her volume according to weight and age.

So what should the Ghanaian government support to reduce the toll in the country from malaria – exotic anti-mosquito campaigns or improved nutrition?

The underlying theory of malaria transmission and the transmission of other diseases by mosquito vectors is that germs enter the female mosquito as part of a blood meal and then develop further in the mosquito before moving to the salivary glands of the animal. When the mosquito bites again, it injects a little saliva that has an anti-coagulant effect prior to having its next blood meal. It is this miniscule saliva injection that supposedly carries the pathogen, plasmodia in the case of malaria, and viruses for West Nile, yellow fever, dengue fever, Japanese encephalitis, etc., from the mosquito to the victim.

And of course, this has become a subject of research. In news-medical.net last week an article was published about research by Anita Saraf, Director of the Mass Spectrometry & Analytical Proteomics Laboratory at the University of Kansas on this topic. Dr Saraf describes how with a new two-year grant of $250,000 per year from the U.S. Department of Agriculture’s National Bio and Agro-Defense Facility, she and her team are currently analysing these samples of non-infectious mosquito saliva in the fight against “arboviruses” a term used for viruses spread by arthropods like mosquitos.

At present they are collecting baseline data to identify the proteins normally present in mosquito saliva (described in the article as shotgun proteomics to analyse biological samples) that can be compared in the future with saliva from mosquitos supposedly infected with the target disease.

Saraf states that “We’ll identify differences and changes at the proteome level by comparing the control and infected samples at different stages. The goal is to determine the protein changes that occur, as these can potentially serve as candidates for vaccine development. We’ll first need to select candidates, which is why we are using controls under the same conditions without infection. We must carefully load equal amounts of protein from both to ensure accurate comparisons -; essentially, we’ll be able to compare ‘apples to apples.”

One of the issues with the belief that malaria is spread by mosquitos is the willingness of many to believe that other diseases are spread by mosquitos. Over the recent labor day weekend in USA there was a scare about West Nile Virus covered sensationally in main stream media. The news articles are the usual fear porn so popular during COVID with the added twist that Anthony Fauci tested positive! There is a belief that the disease is spread by mosquitos. But what is the evidence for this?

Dr Sam Bailey did a deep dive on West Nile Virus in her weekly blog this week. She pointed out that the original diagnosis of the disease was Rockefeller funded research in which blood from a febrile 37 year old woman in Uganda in 1937 was injected directly into the brains of mice (Smithburn et al, 1940). The PCR sequence of the virus itself was supposedly isolated from the brain of a Chilean flamingo (Phoenicopterus chilensis) that died in a zoo in North Eastern USA  in 1999 by Lanciotti et al, who completed genome sequencing of a flavivirus. Most subsequent tests use PCR (Polymerase chain reaction) to find this sequence in the blood of birds, in mosquitos and in mammals (Not unlike the use of PCR and the genomic sequence from one pneumonia patient in Wuhan as the basis for the COVID scare).

Sam Bailey’s article addressed the likely non-existence of the virus and not how it is supposedly spread by mosquitos. And try as I might I could find no references to prove the West Nile Virus mosquito transmission story either. According to CDC (with no evidence)

West Nile virus is most commonly spread to people by the bite of an infected mosquito. Mosquitoes become infected when they feed on infected birds. Infected mosquitoes then spread West Nile virus to people and other animals by biting them.

In nature, West Nile virus cycles between mosquitoes (especially Culex species) and birds. Some infected birds can develop high levels of the virus in their bloodstream and mosquitoes can become infected by biting these infected birds. After about a week, infected mosquitoes can pass the virus to more birds when they bite.

Mosquitoes with West Nile virus also bite and infect people, horses, and other mammals. However, humans, horses, and other mammals are ‘dead end’ hosts. This means that they do not develop high levels of virus in their bloodstream, and cannot pass the virus on to other biting mosquitoes.

Beyond the circumstantial evidence that the PCR sequence is found in mosquitos, birds and some mammals, can anyone direct me to a research article with stronger evidence that this ‘disease’, probably another fictional virus, is spread by mosquitos?

Malaria World this week has a review article by Irish et al published in Malaria Journal, ‘A review of selective indoor residual spraying for malaria control’. Indoor residual spraying (IRS) is described by the authors as one of the most effective malaria control tools. However, its application has become limited to specific contexts due to the increased costs of IRS products and implementation programmes. They review articles on selective spraying targeted to particular areas/surfaces of dwellings, which has been proposed to maintain the malaria control and resistance-management benefits of IRS while decreasing the costs of the intervention.

The basis for the technique is to put insecticides on places within dwellings where mosquitos are likely to rest. When the mosquito lands on the contaminated place it will be poisoned by the insecticide. The article examines if the technique could be more efficient if only the areas, either high or low on the walls or furniture where mosquitos are likely to land are sprayed. It includes references to reviews about where different species of mosquito are likely to land, but most are European studies. The entomological references are similar to the studies carried out by Battista Grassi of the four Anopheles species in Italy that I translated in Studies of a zoologist about malaria.

The studies of this to date for the major African malaria vectors, Anopheles gambiae and Anopheles funestus, have contradictory findings in the literature. In some studies they were mostly on the lower part of the wall and in others on the ceiling. Some of the reported studies compared spraying of DDT at different levels on internal walls in countries including Ghana, Taiwan, Indonesia and the Philippines.

The Taiwan research, a WHO article by Pletsch and Demos from 1954 compared partial and full spraying and reported that Malaria rates dropped from 20% to <1% in Chi san by spraying walls, roofs, ceilings, and undersides of furniture with DDT (2 g/m²). I suspect there were other factors at play in this study. The study was excluded from the 2019 Cochrane review, Indoor residual spraying for preventing malaria by Pluess et al.

Only six of 134 potential studies were included in the Cochrane review article. The Cochrane review concluded that the current evidence is insufficient to quantify properly the effect of IRS in high transmission settings, but stated it seems clear that IRS leads to health benefits.  Available good quality evidence confirms that IRS works in reducing malaria in unstable malaria settings. However, no study investigated the effect of IRS on reducing child mortality. Indeed, it is not clear if the effect on any other health issue other than malaria was considered in these studies.

The belief underlying the research is that IRS played an important role in the elimination of malaria from Europe and USA in 1950s. As I discussed in my book, Malaria is spread by mosquitos?, there were many other improvements to people’s lives that could have caused this improvement in health at that time. I wonder what effect confirmation bias may have had on any of these conclusions? If mosquitos are not responsible for spreading malaria, how would spraying potent poisons inside dwellings aid overall health?