I wasn’t expecting to be writing a blog post at 11 PM but the NEJM just came out with two malaria research studies conducted in a place I care about. And I woke up from a nap from 8pm-11pm. Sleep schedule is erratic with a little baby.
- Article: Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine
- Editorial: Vaccine-Resistant Malaria
- Article: Changing Trends in P. falciparum Burden, Immunity, and Disease in Pregnancy
- Editorial: Declining Malaria Transmission and Pregnancy Outcomes in Southern Mozambique
A few thoughts after having glanced at the articles (admittedly not having read them in any level of detail and not being a malariologist):
- Thoughts about malaria as a non-malariologist
- Dengue and malaria remain the most common causes of travel-associated fever in many series.
- Malaria is a frightening disease and frequently kills people, especially children. Untreated falciparum scares me almost as much as drug-resistant TB/HIV. Not quite, but almost. It makes me not want to travel with my family (especially baby) to Sub-Saharan Africa anytime soon.
- Transmission of artemisinin resistant parasites is a major concern, primarily in SE Asia. Resistance traditionally has been measured by delayed parasite clearance and recrudescence.
- Resistance to insecticides is a major concern in Africa.
- Climate change and increasing population size will have major, unpredictable effects on malaria incidence.
- However, even without climate change, the vast majority of the African continent has excellent conditions for malaria
transmission. And vast swaths of the population have no access to any malaria control interventions (or appropriate treatment).
- Malaria control programs are often weak, especially in comparison to HIV treatment programs. I can’t quote the amount of money spent in PEPFAR vs PMI off the top of my head but I think PEPFAR has disbursed much, much more.
- RTS,S/AS01 Vaccine paper
- As background, remember that this vaccine has low efficacy in young children and major issues with delivery (3 monthly doses, cold chain, etc). It is very difficult to administer to children. It is not a panacea even though some people would like it to be.
- One research site in this study was Manhiça, Mozambique, about 2 hours north of Maputo. I know the town decently well and have blogged about it before. We always enjoy eating the cashews in Manhiça. They are tasty.
- Life is dreadfully difficult for many people living in Manhiça. Not only do they have extremely high rates of HIV and malaria, but schistosomiasis is a major problem as are TB and malnutrition. The economy is very poor and people lack basic health care. Flooding occurs in the region and access to health care is very limited. We wrote a paper about access to health care in a town not far away.
- The other sites in this study are in eastern and western Sub-Saharan Africa (see the map).
- The authors investigated if vaccine efficacy was specific to certain parasite genotypes.
- They found that vaccine has greater activity against malaria parasites with the “matched circumsporozoite protein allele” than against mismatched malaria.
- The Christopher Plowe editorial is useful for those of us who are not malariologists or immunologists.
- Plowe seems quite circumspect — “As this first malaria vaccine moves toward licensure, the results of this study should give pause to those considering whether, where, and when to deploy it. If RTS,S/AS01 is introduced into wide use, over time the loss of efficacy could be more profound than that seen during just a year of follow-up among children who are exposed to a large surrounding population of malaria parasites that are not under selection pressure from vaccine-induced immunity” (emphasis mine).
- I am concerned that a wide roll-out of the current RTS,S/AS01 malaria vaccine could divert attention from other necessary malaria control mechanisms (vector control, etc). There is a major lack of human resources and training in malaria programs in rural Sub-Saharan Africa. In the TB world, the scale-up of Xpert by itself has not been a “game-changer” (yet?). Rolling out technology, like a new vaccine or diagnostic device, requires M&E, training, support, supply chain, etc. Essentially the “staff, stuff, systems etc” that Paul Farmer talks about.
- Without improvements in basic malaria control programs, like bednet coverage, insecticides, etc, a major financially investment/focus in scaling up the current RTS,S/AS01 malaria vaccine could potentially lead to worsened malaria transmission.
- Malaria Transmission paper
- This study took place exclusively in Manhiça, the cashew town. It was a study of rebounds of malaria.
- To really understand this paper you need to be a malariologist. TB/HIV people like me can read it over but we don’t really know what we are talking about especially at 11:30 PM.
- Malaria parasites can persist/ reappear in areas where there is no malaria or it is being transmitted at very low levels
- Declines in malaria transmission and immunity have reduced the malaria burden and adversely affected pregnancy outcomes
- PCR is important in research studies. Smear and RDTs (like “Binax”) are needed for clinical malaria diagnosis.
- The researchers found that “antimalarial antibodies were reduced and the adverse consequences of P. falciparum infections were increased in pregnant women after 5 years of a decline in the prevalence of malaria”
- The editorialist Nicholas White wrote, “reducing the transmission of malaria is clearly good, the concomitant reduction in immunity to malaria increases the risk of adverse consequences for women who become infected during pregnancy. From a public health perspective, there can be no letup in malaria-control activities; otherwise, malaria will return with a vengeance” (emphasis mine).
- Given what I know about the weakness of many malaria control programs and Ministries of Health, I am nervous about this occurring in Manhiça and elsewhere. I feel an obligation to the people of Gaza province because of the research paper we conducted there two years ago and I hope they are able to receive improved health care. Urgency vs complacency, it’s always a challenge.
Thanks so much for reading! Reading/writing blog posts does take significant time and we all know that time is in short supply. You and I will both get much more out of my blog posts if they lead to discussion/dialogue. If you found this post useful and wouldn’t mind leaving a brief comment/sharing on social media, that would be great. Please do remember that blog posts are often written quickly to respond to emerging issues and this one is far from perfect.Thank so much! Best regards, Phil