Just two weeks after reporting that Ivermectin was not effective at preventing malaria, I am surprised to see the lead story in MalariaWorld this week is ‘New research supports ivermectin as an effective strategy to control malaria transmission’.

Ivermectin to Control Malaria —  A Cluster-Randomized Trial by Chaccour et al reports from a study in Kwale, Kenya that children 5 to 15 years of age living in an area with high coverage and use of bed nets, ivermectin, administered once a month for three consecutive months, resulted in a 26% lower incidence of malaria infection than albendazole.

So what is the major difference between the two studies, one of children up to 10 years in Burkina Faso and the other of children 5-15 in Kenya? … The control.

The study in Burkina Faso that did not show a significant effect used a placebo control (no effect) while this study carried out by ISGlobal of Barcelona used an ‘active’ control, another anti-parasitic drug called albendazole, which has side-effects. To quote the study ‘Albendazole, which does not have mosquitocidal properties, was used as an active control to provide these participants with the deworming benefit of ivermectin and to facilitate comparability.’

Dewormers are toxic drugs that poison parasites more that the host. They should not be taken unless one needs to. It continues to surprise me that ‘ethics committees’ approve studies without true placebo controls.

This study was approved by the Scientific and Ethics Review Unit of the Kenya Medical Research Institute, the Oxford Tropical Research Ethics Committee, the institutional review board of the Hospital Clinic of Barcelona, and the Research Ethics Review Committee of the World Health Organization.

And while the study noted that the cumulative rate of malaria infection measured using rapid diagnostic tests was 26% lower with ivermectin than albendazole, there were 65% more adverse events (6.19 vs 3.75 per 100). The authors state that there were no serious adverse effects from 56,000 treatments to justify a recommendation of mass treatment. If tested against a true placebo, would they have found a benefit?

Malaria is much less of an issue in Southern Africa than in my current abode in East Africa. But it was a trip to Botswana a few years ago that first drew my attention to this tropical malady. While my destination near Gaborone in the south was not on the malaria map, Kasane in the north and Zimbabwe, to which I intended to travel were. So my travel companion tasked me with getting malaria prophylactics.

My investigation raised my doubts about malaria transmission story and effectiveness of treatments, so I did not get anything. And we did not contract malaria! The East – South difference in the perception of malaria was confirmed after returning to Ireland when the blood transfusion service declined my donation for 12 months because I changed planes at Addis Ababa in Ethiopia!

But a news story in MalariaWorld this week reports increased malaria in Southern Africa. Africa CDC (Centres for disease control) reports that up to week 23, of 2025, Zimbabwe has reported 111,998 cases and 310 deaths (case fatality rate [CFR]: 0.27%) as compared to 29,031 cases with 49 deaths (CFR: 0.17%) in the same period in 2024. Botswana in same period has recorded 2,223 cases and 11 deaths, compared to 218 cases and no deaths in same period in 2024. Namibia also had a significant rise in malaria cases, with over 89,959 cases and 146 deaths reported since November 2024.

So why the increase which is a reverse of recent trends? Dr Memory Mapfumo, an epidemiologist at the Africa CDC blamed prolonged rains that fuelled mosquito breeding, and activities like gold panning, fishing and artisanal mining are exposing more individuals to risk, especially during peak mosquito activity hours. The belief in infectious disease including mosquito transmission of malaria is core belief of Africa CDC, like its well-known US namesake.

But what if malaria is caused by toxins? I wrote about connection to mining before, and last week visited an artisanal goldmine in Kenya that clearly exposes workers to additional health risks such as finely ground mineral material and various toxic chemicals.

Africa CDC reports low usage of mosquito nets, but this does not explain an increase in cases. Movement of people is also used as an explanation of increase, but it is not clear how. Flooding in Okavango (picture from my visit) increasing mosquito habitat was blamed for increase in Botswana. The possible effect of flooding on drinking water quality was not considered.

In Eswatini 20% of cases were among farmers, many involved in illegal farming activities. These farmers often work at night leaving them exposed to mosquito bites. Or is increase in illness influenced by the effects on health of a disrupted body clock?

It is important to be concerned about the increase of cases of malaria in Southern Africa. However, much as Africa CDC tries, it is difficult to explain the increase in case number by concentrating on the supposed link to mosquitos and ignoring other factors that affect health.

Ivermectin is an anti-parasite medication used to treat parasitic diseases, including parasitic worms, hookworm, whipworm, and external parasites and many others off label. Ivermectin works by paralyzing muscles in parasites, causing them to die. Since malaria is supposedly caused by a plasmodium parasite transmitted by mosquito bites, one might expect this powerful anti-parasitic medication to prevent malaria.

And indeed an article in this week’s MalariaWorld tests this hypothesis. ‘Safety and efficacy of repeat ivermectin mass drug administrations for malaria control (RIMDAMAL II): a phase 3, double-blind, placebo-controlled, cluster-randomised, parallel-group trial’ by Somé et al was published by The Lancet Infectious Diseases. Unfortunately, the full article is behind a paywall, but the summary does provide sufficient information for a preliminary examination and study details are available on clinicaltrials.

The study aimed to test the safety of repeated, high-dose ivermectin mass drug administration (MDA) and its efficacy for reducing malaria incidence among children when integrated with seasonal malaria chemoprevention (SMC) delivery. They provided background that previous studies had shown that ivermectin in the blood could kill mosquitos that fed on it.

They conducted a double-blind, placebo-controlled, trial in southwest Burkina Faso over two consecutive rainy seasons (2019–20). 14 villages were randomly assigned (1:1) to ivermectin or placebo MDA by random draw. Each rainy season, eligible participants from the intervention group clusters received monthly high-dose oral ivermectin MDA (three daily doses, approximately 300 μg/kg dosed by height bands) and those from the control group received monthly oral placebo MDA for up to eight treatment rounds. All participants and study personnel, apart from the pharmacist, were masked to group assignment. The primary outcome was weekly malaria incidence in children aged 10 years and younger, as assessed by weekly active case detection until week 16 of year 2, by intention to treat. Adverse events were monitored in all MDA participants through active and passive surveillance. Blood was sampled for secondary parasitological outcomes, including analysis of parasite species distribution among malaria cases. Mosquitos were sampled from pre-selected households in three clusters per group for secondary entomological outcomes, including analysis of blood-fed mosquito survivorship, mosquito biting rates, and entomological inoculation rates.

The average estimated weekly malaria incidence rate per 100 person-weeks among children in the test group was 1·78 (95% CI 1·24–2·53) and 1·84 (1·29–2·64) in the control group (statistically indistinguishable). The risk of adverse events was lower in test group (arthralgia and skin conditions higher in control group), but risk of death (0.27% vs 0.16%) and serious adverse events greater in test group (0.36% vs 0.31%). There was evidence of mosquito deaths in test group week after test but not three weeks later.

Repeated high-dose ivermectin MDA integrated with SMC distributions at the study site did not reduce malaria incidence among children relative to placebo.

The malaria community was abuzz this week with news of the approval of a drug to treat babies 2-5 kg for malaria. Swissmedic approved Riamet Baby (also known as Coartem baby), the first drug designed specifically to treat malaria in very young children. It is available as a dispersible, cherry-flavoured formulation to help improve administration. A friend alerted me to a BBC news article on July 8 that erroneously referred to it as a vaccine (since corrected). MalariaWorld has link to Novartis Press Release also.

It is a new reformulation of the well-established ACT (artemisinin combination therapy) artemether-lumefantrine. The current paediatric version (pictured) for children ≥5kg on the market, Coartem dispersible, has 20 mg of artemether and 120 mg of lumefantrine. Novartis is the only major producer of artemether-lumefantrine and will benefit for many years from intellectual property protection of this new formulation. I only found one generic version of this ACT, the Indian produced Falcynate LF 80/480mg tablets only suitable for people >35 kg.

Novartis have produced a very readable patient summary of the trial to approve the new formulation and a more detailed summary. The trial included just 28 babies (10 boys, 18 girls) in Burkina Faso (7) and DRC (21), 22 older than 1 month and 6 younger than 1 month who tested positive to malaria parasites whether symptomatic or not. The reason for the reformulation was that in a trial of young babies with 20/120 formulation artemether reached higher levels than expected while lumefantrine stayed at expected levels. Dosing was twice a day for three days by syringe of dispersed tablet in mouth after feeding. Blood was tested at intervals for artemether and lumefantrine. They were also retested for malaria parasites that cleared in 35 hours. Malaria recurred (or was reinfected) in 8/22 of the older babies. The formulation met its design goal and both actives were within expected limits during the trial.

75% (21/28) had adverse events (10 fever, 9 recurring malaria, 7 anaemia, 6 vomiting, 2 bacterial rhinitis). The researchers stated none died and there were no ‘serious adverse events’. However, there was no control. Only five of the babies had fever at the start of the trial and no other symptoms are mentioned. This suggests that the vast majority (82%, 23/28) were asymptomatic. But 75% became sick in some manner in the trial.

The study concludes that the safety profile was consistent with the safety profile of artemether and lumefantrine. Serious side effects include worsening malaria symptoms; severe vomiting, loss of appetite, or being unable to eat; fast or pounding heartbeats; a light-headed feeling, like you might pass out.

Hardly a game changer. Without a control the trial is nearly worthless.

In MalariaWorld this week the study ‘Knowledge, attitudes, and practices regarding malaria in rural Uganda: a cross-sectional study’ by Cathorall et al is featured. In four villages in rural Uganda 106 adults, heads of household, were questions about a variety of issues related to malaria and, in particular, bed net use.

The major findings from this study indicate high rates of net ownership and self-reported use within the rural areas. Perceived susceptibility and barriers were greater among those with a recent diagnosis of malaria within the household. The positive association remained significant after controlling for household size.

Net usage is reported as high. It is difficult to know if the respondents told the truth or what the researcher wanted to hear. However, for comfort why not sleep under a bed net if one is available? I know from experience living in Lodwar, Kenya, and often sleeping outside or with windows open because of the heat that accumulates in houses during the day, that mosquitos will bite exposed skin at night if not excluded by a net. And the bites are uncomfortable.

However, an observation in the study caught my attention. They stated ‘However, only 63 (60%) correctly identified that a mosquito bite was the only way to contract malaria’. I am tempted to ask the corresponding author how they ‘know that’, but I suspect this question is a question of faith analogous to asking a priest or Imam how he knows God exists.

What is curious is the other answers given to these questions by people who live with the disease, showing that some are not convinced by the mosquito tale of the educated westerners. In March 2025 I reported that Chinese expatriates are not convinced either. In the study 42% indicated factors like eating mangos, other foods or bad water as a cause of malaria. Even if they indicated mosquito bites as a risk, they were unsure of the actual route of transmission. The mango theory could be because malaria transmission is seasonal in this region, increasing at the end of the rainy season and coinciding with mango ripening.

The authors suggest that this knowledge gap must be addressed. In surveys in Guinea-Bissau (85%) and Eswatini (99.7%) higher levels of belief in the mosquito transmission hypothesis were measured. I would love to know how they try to convince people of the mosquito hypothesis. I have investigated this topic for years and have found no convincing evidence. Yes, mosquito bites are annoying and uncomfortable, but what is the actual evidence of disease transmission?

An architectural blog article referenced in MalariaWorld provides further support for the linkage of occurrence of malaria to the quality of housing to which I have frequently made reference.  ‘Can better housing help prevent malaria? The Star Homes Project in Sub-Saharan Africa’ by Lonati in designwanted.com describes a custom-built housing project in Mtwara region of Tanzania.

The project started in 2015 when the team noted that traditional rural houses in hot, humid Africa are often built in ways that inadvertently worsen health outcomes: thick walls trap heat, making it uncomfortable to sleep, and ground-level bedrooms and poor ventilation create ideal conditions for disease transmission. They observed that the typology of rural housing in hot-humid Asia differs significantly, despite being in the same climate zone. Houses are often light, air-permeable structures frequently made of bamboo, often on stilts. African houses have earth floor, wattle and daub walls, and thatched, or corrugated iron roofs.

They designed six house types clad in shadenet, timber and bamboo and chose a two-storey shadenet design (picture) which proved the most effective at reducing indoor heat and mosquito entry. However, not insignificantly it had additional features such as rainwater collection tanks, ventilated pit latrines, and washable surfaces to improve hygiene and reduce exposure to disease.

They constructed 110 units of the new Star homes in Mtwara and compared with 440 traditional houses in a study with households of three children to track malaria, respiratory diseases and diarrhoea for three years from 2021. The final report has not yet been published, and preliminary results suggest a 30–40% reduction in malaria among children living in the Star Homes, children under five have shown improved growth, and indoor mosquito abundance has decreased by 50%.

Naturally, much emphasis is placed on excluding mosquitos. The reduction was 50%. There is no doubt that it is more comfortable to sleep if not at risk of mosquito bites. But is the benefit the result of better sleep or less vector borne disease?

And perhaps the health benefit was the result of the other improvements – rainwater collection tanks, ventilated pit latrines, and washable surfaces. Many studies have shown that children who live in better houses are less affected by malaria.

Picture – Ingvartsen Architects © Julien Lanoo

Despite underwhelming performance (see my June 6, 2025 post) the malaria vaccines, that were tested against a rabies vaccine and not a true placebo (see February 8, 2025, December 22, 2024, August 11, 2024, & June 5, 2024) are being promoted heavily in malaria stricken areas, selling people hope that can not be backed by reliable, unbiased studies.

The lead blog in Malaria World this week is ‘How the malaria vaccine came to the world’s most mosquito-bitten district’, a discussion of how Gavi (vaccineswork) is rolling out R21/Matrix-M vaccine in the world’s most mosquito-bitten district, Apac in Uganda. Complete with a YouTube video the promotion is laden with false hope. Children are administered four does at 6, 7, 8, and 18 months), and Dr Odongo, the health officer for the region, stated “We wanted to get on top of any misinformation that could cause hesitancy, and encourage mothers to bring their eligible children for the vaccination”. And the campaign is succeeding with most of the mothers and community leaders in the district as enthusiastic about the vaccine as the health professionals and looking forward to the roll-out.

It reminds me of the enthusiasm in most countries in 2021 for the COVID19 vaccines, and we know how that panned out. They’re even describing it as a ‘magic bullet’. Minister of Health, Dr Jane Ruth Aceng, made the same argument during the April 2 launch. She said that the vaccine was expected to prevent at least 800 cases of severe malaria in children every day.

A research article in Malaria World, ‘Malaria vaccine acceptance and associated factors in Cameroon: A nationwide cross-sectional survey’ by Njoh et al discusses vaccine acceptance. Sadly, the full article is behind a paywall.  In summary, they found 91% malaria vaccine acceptance. This rate varied from 78% in the Littoral to 94% in the Far North and Southwest regions. Factors that favour vaccine acceptance include a history of severe malaria, awareness of the availability of the malaria vaccine for infants and working in the vaccination service. Elements reported for vaccine hesitancy include fear of unsafe and negative rumours about the vaccine.

The authors concluded that people in Cameroon are willing to get their children vaccinated against malaria. However, following regional acceptance disparities and identified hesitancy points, it is crucial to reinforce communication to address population groups, doubts, and rumours about vaccines to ensure optimal uptake in the country’s regions during the malaria vaccine rollout.

Tackling misinformation and disinformation. About what have we heard that lately? Will any of these promoters tell the truth about how the vaccines were tested and how much they, personally, are benefitting financially from the rollout?

Two articles in Malaria World this week describing research in East Africa provide more evidence suggesting that the main factor correlated with malaria is poverty.

‘Household practices and infrastructure associated with high Plasmodium falciparum infection rates among children under five years old in Northern Uganda’ by Echodu et al found housing structures, particularly mud/clay walls and grass-thatched roofs, were significantly associated with higher malaria prevalence (p < 0.001). Children living in houses with cement walls and iron sheet roofs were much less likely to have malaria.

Naturally, the authors linked their findings to hypothesised mosquito transmission by stating that individuals living in houses with intact, plastered walls are less likely to contract malaria compared to those in homes with holes in the walls.

However, the second article, ‘A household randomized-control trial of insecticide-treated screening for malaria control in unimproved houses in Tanzania’  by Odufuwa et al casts doubt on this. In their research, which reminded me a lot of Grassi’s railway study, described in my translation of ‘Studies of a Zoologist about Malaria’, the researchers compared houses with holes fitted with screens to patch holes and those without.

 In Chalinze district, Tanzania, 421 households were randomized into two arms. In June-July 2021, one group of households’ houses was fitted with ITS (insecticide treated nets with deltamethrin and piperonyl butoxide) on eaves, windows, and wall holes, while the second group did not receive screening (see picture). After installation, consenting household members (aged ≥ 6 months) were tested for malaria infection using quantitative polymerase chain reaction after the long rainy season (June/July 2022, primary outcome) and the short rainy season (January/February 2022, secondary outcome).

The results were not significant either in occurrence of malaria (as measured with PCR) or even in the number of mosquitos trapped. The authors suggest this could be due to the study design, intervention insecticidal properties and residuality, and the high number of withdrawals of participants from the study. There was a slight reduction in detection of plasmodia using PCR in the improved houses that was significant for school aged children. However, these relatively insignificant benefits are likely due to the unblinded nature of the study.

So what is the real benefit of living in a better house on occurrence of malaria? It is another clue that clearly links the prevalence of malaria to poverty. Those who can afford a better house can also afford better food, more frequent cleaning and better water and sanitation. Until researchers properly consider these factors, there will not find the real causes and cures of the scourge of malaria.

Malaria vaccines is a hot research topic in Malaria World and is addressed this week in two highlighted news articles and three research papers.

One research paper is a review ‘Malaria Vaccines: Current Achievements and Path Forward’ by Chen et al. It summarises the current establishment views describing the two approved vaccines, RTS, S/AS01(Mosquirix by GlaxoSmithKline) and R21/Matrix-M (developed by Oxford University and the Serum Institute of India). It also introduces 13 other vaccines in development that are described as either Pre-erythrocytic stage, Blood stage or Sexual stage.

One of these, the Pre-erythrocytic PfSPZ vaccine is the subject of one of the news articles, ‘Sanaria reports positive initial safety results for groundbreaking PfSPZ-LARC2 malaria vaccine’. No details are included though the press release says physician-scientists at Groupe de Recherche Action en Santé (GRAS) in Burkina Faso have successfully completed initial safety evaluations in 30 adult Burkinabés as the first phase of a clinical trial of Sanaria® PfSPZ-LARC2 Vaccine, which is designed to prevent infection with Plasmodium falciparum malaria. The initial data of the 30 adults confirmed the vaccine was safe, fully attenuated, and caused no malaria infections. It does not say if a control was used or if there were any side effects.

One scientific paper is an animal study (‘Epitope specificity of antibody-mediated protection induced in mice by the malaria vaccine RTS,S/AS01’ by Flores-Garcia et al) and I will not consider it as it does not address real world efficacy.

The other two articles are not very positive of the effect of vaccines at combating malaria. One is a podcast, The Johns Hopkins Malaria Minute, ‘Why malaria vaccines may work better in some places than others (with Lemu Golassa)’. Professor Lemu Golassa, Head of Medical Parasitology at Addis Ababa University in Ethiopia stated that the RTS, S/AS01 and R21/Matrix-M are unsuitable for combatting he strains of Plasmodium falciparum circulating in Ethiopia.

The research paper ‘Efficacy of RTS,S/AS01E only seen in baseline parasitemic and not baseline aparasitemic Plasmodium falciparum-exposed, drug-treated Kenyan adults’ by Copeland et al found that the RTS,S/AS01 did not prevent malaria in Kenyan adults who did not have the parasite prior to vaccination. There was a modest benefit in preventing malaria in those already infected. However, the control groups in this study received intramuscular injection with a rabies vaccine (Abhayrab®, Human Biologicals Institute, Andra Pradesh, India). This questionable practice was addressed in my first blog post ‘R21 Vaccine is less toxic and ineffective than a Rabies Vaccine’.

Indeed, in this study for the subjects with negative PCRs for malaria parasites, while not statistically significant (-24%, 95% CI; -97 to 22.4; p=0.373) the unadjusted estimated vaccine efficacy is lower for Mosquirix® than for Abhayrab®. The Bill and Melinda Gates Foundation funded study concludes that a vaccine comprising only the CS (circumsporozoite) protein is unlikely to be sufficient to accelerate Pf malaria elimination due to modest efficacy in preventing infection, including in adults. It calls for more research on multi-antigen/multi-stage vaccine approaches that include a CS-component, as well as a one or more blood-stage and/or sexual-stage (transmission-blocking) antigens.

There are a few articles this week in Malaria World discussing accuracy of tests. There are two types of tests is common use. The first is old fashioned microscopy that is considered the ‘gold standard’. A drop of blood is smeared on an microscope slide and it is inspected visually for plasmodia. This method requires a basic laboratory and a skilled trained operator.

The second method is RTD (rapid diagnostic tests). mRDTs (m for malaria) detect the presence of histidine rich proteins released from parasitized red blood cells of a drop of blood. Their use does not require a laboratory or as much training. They have been widely used for routine malaria diagnosis in many rural areas of sub-Saharan Africa.

It is a similar situation to that which applied during the COVID ‘pandemic’. Lateral flow RTDs could be used by anyone and allowed increased testing when compared to PCR (polymerase chain reaction) that was considered the ‘gold standard’. PCR is occasionally used for malaria detection but probably has many false positives (See ‘PCR Detects More Asymptomatic Malaria Cases than RDT’).

The lead article in Malaria World is ‘Researchers question reliability of Abbott’s rapid malaria tests’ by Offord in Science. WHO is concerned that 11 “affected” lots from two Abbott RDTs—Pf/Pv and Pf/Pan—that were associated with “faint lines and false negative results” in reports from “multiple research groups.” They are concerned that the tests do not detect cases especially in Asia. False negatives may be less likely in countries where malaria transmission and parasite densities are higher, as in parts of Africa, says Nick White, a malaria researcher at MORU who is co-authoring an academic paper describing SMRU’s findings.

The second paper of interest on this topic in Malaria World this week is scientific study called ‘Point-of-Care Evaluation of Malaria Rapid Diagnostic Test (mRDT) for Detection of Plasmodium falciparum Among Children Under 5 Years of Age Attending Panyadoli Health Center III in Kiryandongo Refugee Settlement, Mid-Western Uganda’ by Acan et al. The cross-sectional study was conducted among refugee children under 5 years old from February to April 2023. All eligible refugee children aged ≤5 years with suspected malaria symptoms, such as anorexia, vomiting, or abdominal discomfort, with or without diarrhoea, or with a body temperature above 37.4°C or a history of fever within the past 24–48h were included.

380 blood specimens were obtained using the finger prick method and examined for malaria parasites using mRDT (Carestart by Apacor – pictured) and microscopy. A structured questionnaire was used to collect sociodemographic characteristics of the respondents. Data were analyzed using descriptive statistics, while Kappa value was used to provide insights into the agreement between the two diagnostic methods.

The prevalence of malaria using mRDT and microscopy was 12.8% (95% CI: 8.0%–17.8%) and 12.2% (95% CI: 7.4%–17.4%), respectively. mRTD detects a few more cases on average than the ‘gold standard’. But are they mostly the same cases? Cohen’s Kappa Statistic is used to measure the level of agreement between two raters or judges who each classify items into mutually exclusive categories. The concludes that the strong agreement between mRDT and microscopy (Kappa=0.75) further confirms the effectiveness of mRDT as a diagnostic tool. This is considered substantial agreement (0.61-0.80) but not near perfect agreement (0.81-0.99). There is not perfect overlap of the two methods.