A paper in Malaria World this week attracted my attention for additional reasons. The research is organised by University of Notre Dame, where I earned my PhD. It was carried out in Kenya which I will visit next week. I am looking forward to leaving winter behind for a few weeks! The study, by Ochomo et al published in The Lancet, used a double blinded placebo methodology to find that that spatial repellents significantly reduced the hazard rate of malaria infection by ~33%.

The research is sponsored by household chemical consumer good company SC Johnson who are promoting combating malaria with a pyrethroid insecticide, transfluthrin, impregnated mesh product called Mosquito Shield and a similar to product called Guardian (example in picture). The product is intended to repel rather than kill mosquitos.

The study did not contain all the methods and referenced 2022 paper by the same team published in Trials. This paper had more information but not a description of the chemical composition of the placebo (the article stated the trial design included a placebo product of matched design to the Mosquito Shield™ but with inert ingredients only). I am uncertain if this is important and have asked the corresponding author for more information.

The study itself was a cluster-randomised, controlled trial in Busia County, Kenya to quantify the efficacy of the spatial repellent against human malaria infection following mass distribution of insecticide treated nets. Investigators, staff, and study participants were masked to cluster allocation. Infection incidence was measured by microscopy in children aged 6 months to younger than 10 years during a 4-month baseline (March–July 2021) and 24-month follow-up period with intervention (October, 2021–October, 2023). From 58 clusters (29 intervention, 29 placebo), a total of 1526 and 1546 participants from two consecutive, 12-month cohorts were assessed for first-time malaria infection (primary endpoint) by survival analysis at interim and end-of-trial timepoints, respectively.

The two groups were similar, although the placebo group, had slightly more houses with mud walls and on average had fewer windows. This might indicate that cluster locations for the placebo were poorer and poverty is linked to higher incidence of malaria (discussed in a previous post). A weakness of the authors’ hypothesis that the incidence of malaria was reduced by the use of the transfluthrin impregnated mosquito repellent, is that the study did not show that the active repellent caused a statistically significant decrease in Anopheles mosquito numbers.

So is the product effective and if so why? The research used the usual 95% statistical boundary which leaves a 5% possibility the result is not correct. And there is the usual problem with most efficacy studies that the researchers are paid by the beneficiaries of a positive result. If as I suspect, mosquitos, are not responsible for spreading malaria the result can only have been positive because of a structural bias of some sort in the study, or a random false positive result.

Another ‘bug hunter’ paper published in Parasites and Vectors piqued my interest in Malaria World this week. Abas et al captured 20,449 mosquitos between June and December 2023 for ‘Risk of Aedes-borne diseases in and around the Tanzanian seaport of Tanga despite community members being more concerned about malaria’. Most of these (94.9%) were Culex quinquefasciatus or Mansonia uniformis, species not blamed for spreading disease. Only 19 (<0.1%) were Anopheles, the supposed Malaria vector. So the study decided to focus on Aedes Aegypti, 5.1% of the mosquitos captured, that has been blamed for spreading Dengue and Chikungunya. And among other great contributions to science they found that Aedes Aegypti are susceptible to bendiocarb and DDT, and resistant to permethrin. Can you believe they are still using DDT?

What is Chikungunya? It is not a major concern to the 236 residents of the port of Tanga surveyed that was part of the study. A majority 64.8% know mosquitos are blamed for spreading Malaria, 26.3% know about Dengue, but just 1.7% are aware of Chikungunya.

And I must confess, until I read this paper I knew nothing about it. The WHO fact sheet which states that Chikungunya is a disease transmitted to humans by Aedes mosquitos in Africa, Asia, and the Americas. It is similar to Dengue and Zika and so is easy to misdiagnose. Chikungunya causes fever and severe joint pain, which is often debilitating and varies in duration; other symptoms include joint swelling, muscle pain, headache, nausea, fatigue and rash (see picture). Severe symptoms and deaths from chikungunya are rare and usually related to other coexisting health problems.

Of course there is no link to any evidence blaming Aedes mosquitos. In a New England Journal review article by Weaver and Lecuit (2015) there is a reference to Ross (1955) The Newala Epidemic published in the Journal of Hygiene about the isolation of a virus blamed for the outbreak of the of disease, known locally as ‘Chikungunya’, in the Newala district of Tanganyika. The virus was supposedly isolated from human patients and inoculated into mice. Aedes aegypti were allowed to feed on patients but none transmitted the illness to baby mice that they bit later.

However, the authors linked a supposed virus to the illness and found it in a mosquito and concluded The evidence linking the virus isolated to the human disease is very strong. However, there is no evidence of transmission of the disease to humans by mosquito bites.

I have no intention of delving too deep into the virology of this paper. Someone more expert than I can do that. However, it is very clear to me that Koch’s postulates were not met. I suspect that the instinct of the vast majority of residents of Tanga is correct. They don’t need to worry about mosquitos spreading a condition called Chikungunya.

I am not entirely sure what to make a paper listed in this week’s Malaria World. Nor, indeed, are the authors. The title describes the content – ‘Small dams drive Anopheles abundance during the dry season in a high malaria burden area of Malawi’ by Zembere et al published in Medical and Veterinary Entomology. Its very unsurprising finding is that Anopheles mosquito larvae can develop in the shallow shores of the small reservoirs built with clay dams that the residents build to retain water from the rainy season for use in the dry season. Such dams are incredibly important in many parts of Africa to store water for people and their livestock.

This authors carry out a wonderful scientific study incorporating household surveys, indoor mosquito capture, drone image capture (a–d small dam and e–h close-up of an irrigation well and channels) and larval sampling to prove that there are more mosquitos in the dry season near where there are dams. There is no reference to malaria cases, even in the household survey.

The authors in their discussion write ‘What are the practical implications of our findings? Our investigation into the impact of small dams on mosquito populations and malaria transmission aims to inform recommendations for additional vector control that complement frontline tools like insecticide-treated nets. Based on our findings, small dam impoundments provide focal habitat for the most efficient malaria vector in Malawi, and targeting these areas with larval source management (LSM) could have substantial benefits for those communities living within their vicinity.’

The paper, which is mainly entomology, reminds me of Grassi’s research around 1900 that you can read about in my translation of ‘Studi di uno zoolologo sulla malaria’. The underlying assumption is that mosquitos spread malaria.

But what if mosquitos are not responsible for transmitting malaria? It is absolutely certain that water is essential for life and in dry regions of southern Africa dams such as those described in the paper are essential for life. Africa is the driest continent and in many parts conservation of limited water sources is essential. It is of no good if the local population is educated by researchers such as these from Wellcome and the Liverpool School of Tropical Medicine to unnecessarily fear their essential water sources.

Two of the leading articles in Malaria World this week are promoting the roll out of malaria vaccines. One, Life-saving malaria vaccines reach children in 17 endemic countries in 2024, is from the WHO and the other, Malaria Vaccines: Turning a Scientific Triumph into Millions of Lives Saved, is from the Center for Global Development, a globalist thinktank with offices in Washinton DC and London.

This represents a big ramp up in the promotion of vaccines. I remember hearing years ago, before I took a particular interest in malaria, that a vaccine was difficult because the constant evolution of plasmodia from its sexual reproduction life cycle made it challenging. At the time I still accepted medical establishment conventional view of the usefulness of vaccines and had no reason to question this.

But the COVID19 vaccine changed all that. Health authorities promoted experimental gene therapies for emergency use as vaccines for a variation of the common cold (another illness for which vaccines were always said to be a challenge). This overreach encouraged me and many others to investigate the efficacy of vaccines and the germ theory of disease in general which ultimately led me to investigating the story of the transmission of malaria.

But the success of the COVID19 rollout, which was taken by so many people with no good evidence for safety or efficacy, has encouraged the health authorities and the various NGOs and pharmaceutical companies in the network to promote vaccines for other illnesses without convincing evidence of safety or efficacy. These promotions take place without convincing evidence of efficacy or safety using large government and health authority backed information campaigns. I already highlighted that the R21 vaccine was not tested for safety again a placebo but against a rabies vaccine.

The CGD article by Duncomb et al discusses the cost of the GAVIs plan for vaccinate 52m children by 2030, $1.4 billion. It claims that R21, supplied by the Serum Institute in India, is cheaper than RTS,S (Mosquirix from GlaxoSmithKline), the first vaccine rolled out, at around one third of the cost. The authors claim 75% efficacy against clinical malaria in perennial (i.e. non-seasonal) sites in children aged 5-17 months. The linked pdf references the 2024 Lancet article ‘Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial’ by Datoo et al.

Yes indeed, the same article I already addressed that found that children in Burkina Faso were less likely to get malaria after R21 vaccine that after the Abhayrab rabies vaccine! it was not compared to a placebo.

A very interesting article was listed in news-medical.net this week. The open access article called ‘Animal-sourced foods improve child nutrition in Africa’ by Khonje and Qaim used representative data from five African countries—Ethiopia, Malawi, Nigeria, Tanzania, and Uganda—to show that the consumption of animal-sourced foods (ASF) contributes to improving child nutritional outcomes and that these positive effects cannot always be provided by plant-based foods alone. This counters the general calls to reduce ASF consumption for more sustainability. The authors consider that this call to lower consumption of ASF is not fully applicable to Africa, where average ASF consumption is low.

The article compares the effect on the health of children of the consumption of ASF and nutritious plant-based foods (NPBF) such as legumes, fruit and vegetables. Stunting is more common in Africa where nutrition for children is often inadequate and consumption of ASF is low. Consumption of NPSF does not reduce the likelihood of stunting as much as consumption of ASF. Eggs are the most effective ASF for increasing the height of children and reducing stunting. The authors also make the point that ASF is more likely to be available year-round. Much nutritious plant-based food is seasonable and less available in rural Africa due to poor infrastructure and refrigeration facilities.

While malaria is not mentioned in the article, in earlier posts and in my book ‘Malaria is Spread by Mosquitos?’ I have referred to the fact that incidence of malaria is linked to malnutrition. I have little doubt that if a study were carried out of the effect of the incidence of malaria on consumption of ASF it would have a very positive and statistically significant result.

Two articles in Malaria World pertaining to the two countries with the largest numbers of deaths attributed to malaria caught my attention. The first is the lead article, a BBC report about vaccine rollout in Nigeria the most afflicted country with 26.8% of deaths. The article describes the roll-out of the new vaccine called R21/Matrix-M which started in two of the worst-affected states – Bayelsa and Kebbi. It is planed is to expand it to the rest of the country by next year.

R21/Matrix-M, developed by the Jenner Institute at Oxford University, uses three doses administered four weeks apart and a booster dose given after one year. In an earlier article I described that it was not tested against a true placebo, but was compared for side effects against a rabies vaccine. My email to WHO and UNICEF asking if they had any other evidence to justify dosing malnourished children in Southern Sudan with the R21 chemical concoction received no response. Oxford was also the place the Astra-Zeneca COVID19 vaccine was developed and that did not turn out too well in the end.

Another article in Malaria Word by Alhassan et al, is Call for elimination program of Malaria among children under 5 years old living in refugee camps in eastern Democratic Republic of Congo. DRC is number two for malaria attributed deaths with 12.3% of worldwide malaria deaths. The article’s message is typical, a call to boost the traditional malaria interventions of distributing insecticide-treated nets and drugs, by improving vector control, improved diagnosis and treatment capabilities, and strengthening local health systems.

But the article in its discussions does provide important clues about why malaria is serious in deprived parts of the DRC. The authors state that refugees are more susceptible to contracting malaria infections by their lack of protective immunity, increased concentration of people in endemic settings, limited resources, their poor exposed living conditions, residing in unfinished houses, poor drainage and acute malnutrition among the children due to inadequate food rations. However, instead of proposing activities to improve these unhealthy living conditions the authors call for more of the usual supposed solutions – more testing, more poisons for people and more poisons for insects.

A very interesting article in Malaria Journal by Ashton et al, Efficacy of attractive targeted sugar bait stations (ATBS) against malaria in Western Province Zambia: epidemiological findings from a two-arm cluster randomized phase III trial, describes a large real world trial of the efficacy of sugar baits affixed to the walls of buildings laced with clothianidin-deltamethrin (Fludora® Fusion,Bayer) at preventing malaria. Mosquitos live on nectar and other natural sugar sources. Female mosquitos only require a blood meal as extra nutrition prior to laying eggs.

This study actually looks for the incidence of malaria. Previous studies showed that such baits could reduce the prevalence of Anopheles mosquitos by up to 90%. And in this detailed study with over 120,000 target population evenly split between test and control groups, the use of ATSBs did not statistically reduce the number of cases of malaria identified clinically or by RTD tests of plasmodia. And compared to the control arm, the ATSB arm had higher reports of eye irritation, although the DSMB (Data Safety Monitoring Board) determined that these adverse events were not related to the intervention.

The authors report that results of similar studies in Mali and Kenya are in preparation. The question that probably did not cross their minds, is whether mosquitos actually spread malaria, so how would killing them affect the incidence? Could this be the reason the study did not demonstrate a statistical reduction of malaria incidence?

This week I introduce similarities and differences of the approach to AIDS and Malaria in Africa. African friends express more concern about AIDS and HIV. In many cases that have known victims and it seems a more real threat. I have not examined HIV/AIDS in any great detail as many others more qualified on the topic than me have been examining the truths of it since Gallo and Montagnier first launched this new disease on the world in the 1980’s. Peter Duisberg, The Perth Group, Mike Stone in viroliegy, and many other have examined the weaknesses of the establishment case as presented in Wikipedia or by the UN in much more detail than I ever could. I recommend Virus Mania by Engelbrecht et al as a good first read on this and other diseases.

Similarities are ~600,000 annual worldwide deaths, both are usually ‘diagnosed’ with a variety of non-specific symptoms and a Rapid Diagnostic Test (RTD), and both diseases are more likely to affect the malnourished and otherwise deprived. The major difference is that HIV/AIDS is supposedly transmissible between people, usually sexually, whereas Malaria requires a vector. HIV/AIDS is more likely to affect adults whereas Malaria affects children moreso.

The telltale AIDS illnesses such as Kaposi’s sarcoma were common in Africa a long time before the supposed discovery of HIV and AIDS. And from 1985 until ~2000 AIDS was not diagnosed in Africa without the anti-body test, but with a variety of conditions that were not unusual. The ‘Bangui Definition’ diagnosed AIDS if the patient had three of four major clinical signs – loss of body weight (>10%), chronic asthenia (weakness), chronic fever and chronic diarrhoea. AIDS is notable for having widely definitions depending on country.

The supposed sexual transmission adds greatly to the stigma about HIV, especially for females, a majority of test positives in Africa. Pregnancy and other conditions often cause positive HIV tests. However, sexual transmission has not been proven. The best evidence, in particular the Padian 1997 study suggests it is not.

The cure is much worse than the disease to a much greater extent than for malaria. Many working in the field suspect that poor quality anti-virals dispensed to patients cause them harm. Many who have examined the early celebrity victims of the 1980-90s (Rock Husdon, Freddy Mercury, Rudolf Nureyev, Arthur Ashe) feel that the drugs they took contributed significantly to their demise.

HIV/AIDS is big business. The 2024 UN global AIDS Update is a large book emphasising sexual health and drugs dispensing. Of course, like many conditions it would be eliminated in the morning with one simple act – stop testing for it. But then of course they might have to attend real issues.

Malaria World this week featured the news –  New drug could help fight against treatment-resistant malaria. The article referenced by Scottish  researchers Brettell et al was published in the Journal of Medicinal Chemistry and is entitled Targeting Pf CLK3 with Covalent Inhibitors: A Novel Strategy for Malaria Treatment.

In summary, the novel compounds developed inhibit the development of Plasmodium falciparum plasmodia by inhibiting the enzyme Plasmodium falciparum cyclin-dependent like protein kinase-3 (Pf CLK3), one of a family of four protein kinases with a role in the phosphorylation and assembly of components of the RNA spliceosome. The paper includes a detailed description of the chemistry including synthesis, molecular structures and an in vitro comparison of efficacy with artemisinin at inhibiting development of plasmodia.

The paper is impressive looking with detailed graphics. The research at the University of Glasgow was carried out in association with Keltic Pharma Therapeutics Ltd who are partners of Bill and Melinda Gates Foundation and Control Malaria.

Most common malaria treatments are now generic drugs. Developing new, supposedly effective, drugs is important to the pharmaceutical industry to maximise profits.

But obviously a drug with a mechanism such as this is only going to be effective at curing malaria if the Plasmodium infections it targets are the cause of illness.  If they are the clean-up crew as I and other ‘terrain theory supporters’ believe, inhibiting their development is not going to benefit the patient and may even cause harm.

For the second time in recent weeks, I am glad to report that some malaria researchers are questioning the use of insecticides to combat malaria. A proof copy of a review paper by Oberlin et al entitled ‘Effect of Indoor Residual Spraying on Malaria in Pregnancy and Pregnancy Outcomes: A Systematic Review’ was included in Malaria World this week. The authors screened 1,845 abstracts and included 17 articles in their review, one in India and the others from various African nations.

There was confounding of different methods in the studies – IRS, IPTp and bednets. In nine of the 17 studies the insecticide used is not identified. Some studies looked for parasites. Others relied on self-reporting of symptoms, which can be subject to bias. Three studies claimed to detect a reduction in placental malaria in those exposed to IRS.

Just five studies examined pregnancy and neonatal outcomes. One study only showed a significant benefit in the group exposed to IRS for 90% of the pregnancy. Conversely, another showed a significant INCREASE in preterm births (PTB) in those exposed to IRS during pregnancy. Some studies showed a decrease in low birth weight (LBW) when exposed to IRS during pregnancy but not all. There were mixed results to the question of a reduction of fetal and neonatal fatalities.

However, one study evaluated the risk of external urogenital birth defects in male infants born to mothers exposed to IRS and found the risk of any urogenital birth defect was 33% greater in those exposed to IRS. Only five of the studies were considered good, including the two studies that found the most negative results. Most of the studies examined were considered fair or poor.

The authors concluded ‘…without high-quality evidence to understand the potential risks and benefits of its use, no clear endorsement of its use to protect pregnant women can be made. Caution is also warranted given demonstrated negative long-term impact on childhood neurodevelopment from prenatal exposure to certain insecticides’.

[picture from www(dot)swissmalariagroup(dot)ch]