I Was Dumbstruck with Imposter Syndrome

At a social gathering in Nairobi this week the subject of Malaria prophylaxis was raised and I said nothing. And it bothers me. A European, who does not take anything to prevent malaria in Nairobi, asked some Kenyans about getting malaria tablets for a trip to Mozambique. They discussed that tablets could be obtained and even commented on how sick one gets from Malarone™ (GlaxoSmithKline atovaquone/proguanil HCl). The first line in medscape review is – In event of vomiting within 1 hour of dose, repeat dose!

And I said nothing. Why? I did not go to the gathering to discuss malaria. I am networking looking for engineering work in Nairobi. Was it cowardice – fear of discussing a controversial topic that may alienate potential clients? Or was I unprepared? I resolved to prepare a 30 second ‘elevator pitch’ on the topic. Afterall, it was the consideration of prophylaxis that started me on my journey studying malaria.

Or did I feel like an imposter? Wikipedia defines Impostor syndrome as a psychological experience in which a person suffers from feelings of intellectual and/or professional fraudulence. Being Irish what would I know about malaria?

But I have become the expert in this field in the world. I love the approach of Daniel Priestly, to become a KPI (Key Person of Influence) in your field.  While Daniel’s focus is on developing money making business, being the world’s leading expert on malnutrition as the major cause of malaria (and mosquitos and plasmodia not being a cause) is the opposite of a lucrative business opportunity. Selling drugs and insecticides to combat malaria, according to the conventional paradigm, is big business for Western, Indian and Chinese companies. Many researchers and medics are employed in malaria treatment and research.

As a mzungu (Swahili for white man) with a PhD and extensive medical industry experience I have credibility to question the narrative. The malaria transmission story was developed by other mzungu (Laveran, Ross, Grassi and others) against the instincts of many affected people. I am the first to translate Grassi’s work from Italian. I have written the most comprehensive book on the topic. I write a weekly blog on malaria research looking for clues for the malnutrition cause and obvious flaws in the conventional approach (this week GAVI are celebrating getting Ugandan minister to agree to vaccine roll-out).

I will not be dumbstruck on this topic again. I resolve to promote my understanding of malaria and the flaws of the conventional approach more strongly. At a later meeting this week I expounded my thoughts to a pharma industry person who asked me about my malaria research. I will make presentations for free to any gathering. I am a distinguished toastmaster and TED speaker and I guess I have found my vocation.

Malaria Researchers Refuse to Consider Link to Food or Water

A few articles caught the eye in Malaria World this week. Firstly, the US FDA has placed a clinical hold on COVID vaccine maker, BioNTech’s early-to-mid stage trial of an experimental RNA malaria vaccine. Curiously, no reason was given for the hold on the Phase I/IIa study testing BNT165e in nearly 180 healthy and malaria-naïve adults to primarily assess the safety and tolerability of the experimental shot, while also looking for signs of efficacy and immunogenicity

Secondly, ‘Subnational tailoring of malaria interventions to prioritize the malaria response in Guinea’ by Diallo et al examined attitudes only to chemical interventions – Indoor Residual Spraying, IG2 insecticide treated bed nets (see picture), seasonal malaria chemoprevention, perennial malaria chemoprevention (also known as intermittent preventive treatment for infants) and RTS,S vaccine. Clearly, better food or water are not considered as potential factors at reducing malaria.

And finally this is spelt out very clearly in ‘Survey on knowledge, attitudes and practices (KAP) of malaria prevention and control among Chinese expatriates in South Sudan’ by Su et al. In the survey of Chinese workers in South Sudan 99.0% ‘know’ that female Anopheles mosquito bites can transmit malaria. However, the authors report that ‘some respondents (21.64%) erroneously believe that contaminated food and water sources can also transmit malaria’.

Later, they state that ‘53.23% of respondents mistakenly believed that attention to food and drinking water hygiene could prevent malaria’. I consider it very promising that a majority of Chinese workers (the vast majority in South Sudan for < 1year) realise that attention to food and water could prevent malaria, despite the attitude of the malaria researchers. The authors, without any cited evidence, dismiss the link to food and water with the words ‘erroneously’ and ‘mistakenly’.

To again quote Upton Sinclair “It is difficult to get a man to understand something, when his salary depends on his not understanding it.” And so long as malaria research is flooded with funding from producers of chemical solutions to poison mosquitos and people, the nutrition and water hygiene connection will be suppressed in peer reviewed research.

Effect of Human Activities on Malaria Positivity

I continue my visit to Kenya (back in Nairobi) and by coincidence the most interesting article in Malaria World this week relates to Kenya and was carried out by researchers from KEMRI, whose meeting I reported recently. ‘Impact of Titanium Mining and Other Anthropogenic Activities on Malaria Positivity Rates and Parasitemia in Five Selected Study Sites in Msambweni Subcounty, Kwale County, Kenya’ by Githinji et al studies Plasmodium positivity by RTD and microscopy in five villages. One village had titanium mining activities (Mwaloya), one sugar cane farming (Fahamuni), one had a dam (Marigiza), another had all three (Gonjora) and the fifth, the control (Mafisini), had none of these three human activities.

The results were quite clear especially comparing the village Mafisini (11.0% by RTD) with none and Gonjora with all three (33.7% by RTD). The villages with one activity had intermediate values. Mining, despite its prominence in the title, had the least effect (Mwaloya 17.6%) followed by Dam (Marigiza 23.3%) and Sugar cane farming (Fahamuni 26.8%).

No other differences between the villages were mentioned (e.g. poverty) and the authors admitted to limitations of the study. All of the explanations of the differences were linked to effect on mosquito habitats demonstrating the acceptance of the researchers of the conventional transmission model. The dam is a breeding ground for mosquitos. Sugar farming requires tilling of the land that results in additional pools in which mosquitos can breed. Mining requires the use of earth moving equipment that also results in pools for mosquito breeding. On the positive side, the wealth from mining pay packets, can benefit with improved houses and ability to buy malaria deterring items like bed nets. This explains why mining is the least bad of the three activities.

But what if mosquitos are not a factor in the transmission of malaria? We could explain the effects on increased positivity due to possible additional environmental toxins from these activities. The villages with a dam use potentially contaminated surface water instead of cleaner ground or piped water in areas without dams. Sugar cane farming uses a lot of pesticides. Mining operations use and unearth many toxic materials. And adding all three together could have a big additional effect.

Malaria. A Real Case?

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.

Asymptomatic Malaria

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?

KEMRI KASH Conference. Day 2 Review

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.  

Vaccines – Major Topic of Malaria Research

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.

Occurrence of Malaria associated with Poverty – Tanzania Study

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.

Single-Dose Malaria Vaccine Offers Unprecedented 90% Protection?

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.

Is Malaria a Problem in Kenyan Central highlands?

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.