I continue my stay in Kenya in Lodwar, Turkana, a desert area where many roads are like sand dunes and temperature usually reaches 40C each day. I was going to write about how annoying mosquitos are. One morning I awoke with five bites on my right little finger. I bought a bed net next day.

Perhaps only a resident of a mosquito free country like Ireland could have written in defense of such an annoying beast!

But in the wee hours of Tuesday morning my friend suffered from serious chest pains and we attended local A&E. Routine blood tests for infection and a microscope slide for Malaria plasmodia were negative. They prescribed a mild opiate painkiller and amoxicillin antibiotic anyway. Later that day my friend vomited and pain went away.

However, it returned suddenly three days later. This time we attended a small private hospital. Immediately the patient had a nice gurney and was put on painkilling drip from start. The same routine blood tests, but this time positive for malaria (malaria test was RDT and level detected very low). Hydration drips were administered and pain eased and moved to stomach. We suspected aggravation of gastric nerve was cause from diet or other reasons.

But lastly administration of artesunate injection, Argesun, and appointments to return for two more at 12 and 24 hours. And a follow up course of artemether-lumefantrine tablets.

And side effects of artesunate include stomach pain and nausea/vomiting, which were the main symptoms of the illness.

So what changed in the three days? The symptoms were not classical malaria symptoms. But a positive test for plasmodium generates this response.

How real is malaria? It seems to be a disease of any symptom, just so long as there is positive plasmodium test.

The gulf between me and the allopathic medical establishment (and its belief in germ theory) was very clear at the poster session of Kenya Medical Research Institutes Annual Scientific and Health Conference. Maurine Mwalo presented the paper by Obilo et al, ‘Updating Malaria Risk-Map of Kenya Through Diagnosis of Asymptomatic Malaria-Infected Individuals’. Just 3.6% of 13,719 tested were positive for plasmodia. And of these 490, 99.5% had no symptoms. They were treated with the ACT Artemether-Lumefantrine anyway.

I asked how it could be said that these 99.5% asymptomatic positive individuals had malaria if they were not ill. The presenter and the rest of the audience all said in unison ‘They have the parasite!’. It reminded me of the recent COVID war and the obsession with positive test results whether patients had symptoms of illness or not.

And this week Malaria World features a review paper ‘The Burden of Asymptomatic Malaria Infection in Children in Sub-Saharan Africa: A Systematic Review and Meta-Analysis Exploring Barriers to Elimination and Prevention’ by Asmelash et al. The results of 24 studies were combined and found 25% prevalence of asymptomatic malaria in children 6 months to 15 years. The two notable findings were that children who tested positive were 3.53 times more likely to be anaemic, and families who never or sometimes used ITN (insecticide treated nets) were 3.89 times more likely to have asymptomatic malaria compared to families who usually utilized ITN. The study also revealed that the prevalence of asymptomatic malaria was not significantly associated with stunted children.

The authors state that anaemia is a symptom of malaria and the ITN result is proof of the effectiveness of nets for excluding mosquitos and preventing malaria transmission.

This paper is a good example of the confirmation bias present in every study of malaria since the time of Ross and Grassi. There are other possible explanations for the results if one does not try to fit them to the mosquito-plasmodium transmission theory.

I suspect that malaria is an illness caused by malnutrition. If a person becomes quite ill, plasmodia present in the blood will multiply to consume the dead tissue, especially blood cells of the ill individual. If well (asymptomatic) these plasmodia will remain dormant and undetectable in the healthiest people. But people who may be a little run down might have more, a detectable number. The coincidence with anaemia is not surprising. If red blood cells are breaking down (anaemia) plasmodia will start to multiply.

And the ITN result may be a marker of other factors, in particular, the economic status of the family. I expect better off families are more likely to have and use ITNs. They are also more likely to be able to afford nutritious food and clean water.

And the bottom line is that people without symptoms and not actually ill. How can an asymptomatic person be said to have malaria?

On 12 February I attended Kenya Medical Research Institutes Annual Scientific and Health Conference (11-14 Feb) which had sessions on malaria. The conference was held in the magnificent Safari Park Hotel in Nairobi and included plenty of food and a lovely lunch. And I got a nice bag (picture).

However, this was very much a medical establishment event and as a medical heretic I was either a fox in a henhouse or a chicken in a fox den!

The keynote address was by Feiko ter Kuile of Liverpool School of Tropical Medicine who discussed their long-established research base in Kisimo that has grown from 50 to 450 researchers.  He expressed concern about the Trump USAID actions. A research topic he discussed was SP (sulfadoxine-pyrimethamine) resistance and said DP (dihydroartemisinin‐piperaquine) had most potential, but SP is still better at preventing severe malaria. DP is a newer ACT not addressed in my book ‘Malaria is Spread by Mosquitos?’ and I will examine it in more detail later.

There were no topics of great interest at the morning scientific sessions. The main malaria session had a variety of the usual scientific topics highlighted in Malaria World each week. There was one talk about the evaluation of nutrition improvement for children 0-36 months in Rising Star session. However, I missed the talk and malaria is not mentioned in title.

I did ask both sessions if any of the presenters were aware of research on the effect of improved nutrition and clean water on the severity and occurrence of malaria and got no answer. One delegate did talk to me at the lunchbreak intrigued by my question.

The gulf between me and the allopathic medical establishment (and its belief in germ theory) was very clear at the poster session. Maurine Mwalo presented the paper by Obilo et al, ‘Updating Malaria Risk-Map of Kenya Through Diagnosis of Asymptomatic Malaria-Infected Individuals’. Just 3.6% of 13,719 tested were positive for plasmodia. And of these 490, 99.5% had no symptoms. They were treated with the ACT Artemether-Lumefantrine anyway.

I asked how it could be said that these 99.5% asymptomatic positive individuals had malaria if they were not ill. The presenter and the rest of the audience all said in unison ‘They have the parasite!’. It reminded me of the BS with COVID positives.

I attended a Symposium on tackling climate-driven zoonotic disease threats in East Africa. Topics included Ebola, Rift Valley Fever and Brucellosis. I don’t believe in viral illness but had no interest in getting involved. Brucellosis is a disease of cattle in Ireland but I have not heard of it being spread to humans. Curiously, its symptoms seem similar to malaria – 1) fever, 2) Another generic symptom, 3) positive test (for Brucella bacteria). Older people with symptoms are less likely to test positive than the young. I suspect that the bacteria, much like plasmodium in malaria is not the cause of the malady.  

I continue my visit to Kenya, now in Nairobi, and have now seen and been bitten by mosquitos. Unpleasant, but not a disease threat. With a planned visit the Turkana the article in Malaria World reporting ‘Prevention Trial Cuts Malaria Cases in Children by 70 Percent’ by a team from Duke University led by Duke Global Health Institute professor Wendy Prudhomme O’Meara caught my attention. However, it was only a preliminary report. I asked Dr O’Meara for a research paper to review the details of the methods and analysis. She promptly and politely responded that publication was delayed by current funding crisis related to the future of USAID.

So instead my attention was drawn to the subject of vaccines, which I have addressed before, (here, here, here, here and here), but not to any particular article. But rather to the number of articles (six). The first is a press release from WHO, ‘Child health improves in Cameroon one year after malaria vaccine introduction’. A 20% reduction in cases from 2023 to 2024 is reported but there is no clear linkage to the vaccine. And of course correlation does not imply causation.

The second (and first research paper) ‘Acceptability of the R21/Matrix-M malaria vaccine alongside existing malaria interventions in the trial context’ by Diawara et al examine the acceptability of the R21/Matrix-M vaccine in Mali. They found it generally acceptable but article adds nothing on safety of effectiveness.

The third  ‘Malaria vaccine introduction in Africa: progress and challenges’ by Impouma et al. This Lancet article discusses the roll-out of malaria vaccines RTS,S/AS01 and R21/Matrix-M in the first year of malaria vaccine implementation, examining achievements, challenges, and strategic opportunities. A discussion article adding little new.

The fourth ‘Genetically attenuated parasites show promise as a next-generation malaria vaccine’ by Hafalla et al discussed genetically modified parasite use in vaccine. I covered this topic recently here. It is early stage of experimentation.

The fifth ‘Malaria: Factors affecting disease severity, immune evasion mechanisms, and reversal of immune inhibition to enhance vaccine efficacy’ by Su et al is a review of the challenges developing malaria vaccines.

The sixth ‘The R21/Matrix-M malaria vaccine: questions remain’ by Aaby et al has the most interesting finding. In a letter to the Lancet they report that supplementary material of Dattoo study previously discussed reports 18 deaths—15 in the experimental group and three in the control group and state it is not significant. The statistics reported suggest otherwise (relative risk 2·50, 95% CI 0·72–8·62; Fisher exact test, p=0·21). They also state that it is important to know the correct number of deaths in both the vaccine and the control group and by sex.

And note – the control group was not even a true control, but recipients of a rabies vaccine.

I continue my work in Kenya this week near the Tanzanian border (picture of marker in Masai Mara national park) and an interesting article about the occurrence of malaria in Tanzania was listed in Malaria world this week. ‘Prevalence and­ drivers of­ malaria infection among ­asymptomatic and­ symptomatic community members in ­five regions with­ varying transmission intensity in ­mainland Tanzania’ by Chacha et al published in Parasites and vectors was carried out in July-August 2023, funded by Bill and Melinda Gates Foundation.

The study tested 10,228 individuals in Kagera, Kigoma, Njombe, Ruvuma and Tanga using rapid diagnostic tests (RDTs). There were differences between districts – varying 21.6% in Tanga to 44.4% in Kagera. There were differences between villages, males had higher positivity than females and school age children had higher rates than under-fives and adults.

Individuals from households with low socio-economic status (SES), or living in houses with open windows and/or holes on the walls, and non-bednet users had statistically higher rates of positive RTD tests (41.5% vs 32.2%). Positive test results were significantly higher among individuals living in households with five or more people (35.4%) compared to those with fewer members (30.0%). Individuals from households with low SES had significantly higher malaria prevalence (37.9%) than those with moderate (33.3%) or higher SES (31.3%). The type of walls of the houses had an effect, where individuals living in houses whose walls were made of mud exhibited a higher prevalence (37.1%) than those from houses constructed with bricks (32.9%). The presence of holes in the walls (39.2%) and open windows (36.3%) had higher prevalence of malaria infections.

The authors link these factors to vector control strategies. Open windows and mud walls are considered more porous to mosquitos. But what is significant is that poor quality of houses and ownership of bed nets are likely factors that correlate with poverty. However, it should be pointed out that most ‘cases’ are asymptomatic, so most people are not really ill.

Malaria disappears from countries when living standards improve. The authors note that the Ministry of health reports a decrease in incidence of malaria in Tanzania. The percentage of children under age 5 who tested positive for malaria according to RDT results has generally decreased over time, from 18% in the 2007-08 Tanzania Health Ministry Indicator Survey (THMIS) to 8% in the 2022 Tanzania Demographic and Health Survey and Malaria Indicator Survey (TDHS-MIS). Also reported is that the percentage of children under age five who are malnourished has decreased steadily from 48% in the 1999 TDHS to 30% in the 2022 TDHS-MIS. And as the country’s economy improves malnutrition will decrease and malaria will eventually disappear completely. This will have nothing to do with anti-mosquito interventions.

After one week in Kenya volunteering to help maintain a Masai village water scheme, I have heard no mention of malaria, nor seen, never mind being bitten by, a mosquito. So I will address a paper highlighted in news-medical.net ‘Single immunization with genetically attenuated PfΔmei2 (GA2) parasites by mosquito bite in controlled human malaria infection: a placebo-controlled randomized trial’ by Roozen et al at Leiden, Netherlands published in Nature Medicine. The paper was listed two weeks ago in Malaria World.

In this double-blind placebo study fifteen malaria-naive participants aged 15–30 years were enrolled at Leiden University Medical Centre, Leiden. They were vaccinated by being bitten 50 (±5) times with GA2-infected (10 test subjects) or uninfected Anopheles (5 control subjects). Six weeks later, all participants underwent controlled human malaria infection (CHMI) through the bites of five mosquitos infected with unattenuated homologous wild-type Pf parasites. In subsequent visits they found that 9 of 10 (90%) participants in the GA2-MB group were fully protected against Pf malaria and remained PfqPCR-negative until day 28 post-CHMI. By contrast, all participants in the placebo group became parasitaemic (log-rank test P < 0.0001). This is using a PCR amplification technique.

However, there was no notable difference in symptoms between either group at any stage, so while the technique does prove that the test subjects dosed with a vaccine administered with 50 mosquito bites by mosquitos infected with genetically attenuated Pf sporozoites, were less likely to have wild Pf sporozoites in their blood than control patients who suffered 50 bites by uninfected Anopheles stephensi mosquitos. They were no more likely to become ill. But I would not expect healthy young Dutch adults to become ill, unless also malnourished or poisoned.

The test mosquitos were infected using a membrane technique (reference Ponnudurai et al 1989 – behind paywall) in which mosquitos in a jar can ‘feed’ on the test blood through a membrane (see image), which had the genetically modified plasmodium added.

As the authors admit, the study is limited by the small sample size of healthy malaria-naive participants who do not adequately represent the target population for malaria vaccines in endemic areas. And administration of GA2 through mosquito bites is not a feasible method for large-scale immunization campaigns.

This study is a remarkable scientific endeavour. And IF malaria is an infectious disease caused by a plasmodium germ transmitted by mosquito bites, this might be a breakthrough against malaria. However, this is far from certain and based on the assumption of the validity of germ theory instead of terrain theory for the occurrence of disease.

Picture from UNC Medical website.

I travel to Kenya this weekend, so naturally in Malaria World my attention was drawn to ‘Malaria prevalence, transmission potential and ­efficacy of­ artemisinin-based combination therapy in­ the ­Kenyan Central highlands: a­ zone previously characterized as­ malaria-free’ by Kimani et al. This is a large study with many components carried out in Kikuyu sub-county of Kiambu County, Kenya located about 20km Southwest of Nairobi, part of the Kenyan Central highlands.

In included mosquito sampling in houses and of larvae in swamps (see picture). It included non-randomized 28 day, uncontrolled clinical follow up with one treatment arm to assess the efficacy of artemether-lumefantrine (AL). Blood was examined for plasmodium parasites. They looked for ACT (artemisinin combination therapy) resistance markers using gene analysis.

And the results. Only two adult Anopheles mosquitos were collected indoors from 30 houses over three nights (and in the one house). And they were negative for plasmodia. More were hatched and reared from larvae collected in the swamps (148 female Anopheles).

In the hospital just 5.6% of 838 patients with malaria symptoms had positive slide results for plasmodia. All received a dose of the drug.

The authors do conclude that the positivity rate was very low. However, they interpret the results as presenting a changing situation that may require further research. They did conclude that the parasites were susceptible to the drug.

I must admit I found this research very underwhelming. The area of Kenya examined was not the North East like Busia near Lake Victoria I discussed last week that has more malaria. It is convenient to Nairobi for the KEMRI researchers. I suspect if a similar study were carried out practically anywhere it would find similar numbers of Anopheles and similar level of plasmodia in patients with malaria symptoms. Or maybe even more. There have been no major outbreaks of malaria in this region since 1980s and 1990s, just anecdotal reports that residents of the area have been treated for malaria. And malaria is an illness with symptoms common to many other ailments.

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.