Category Archives: Monkeys

Malaria News Today 2020-09-21: Vectors, Cities and Chimpanzees

First we look at how disease can influence urban planning. We have four news stories focus on field activities for vector control from Hyderabad, India, Borno State, Nigeria, Papua New Guinea and CHAD. Finally there is an ancestry article of sorts examining plasmodia in chimpanzees and humans. Click on the links to read full details.

Can Covid-19 inspire a new way of planning African cities?

Health crises are not new in Africa. The continent has grappled with infectious diseases on all levels, from local (such as malaria) to regional (Ebola) to global (Covid-19). The region has often carried a disproportionately high burden of global infectious outbreaks.
How cities are planned is critical for managing infectious diseases. Historically, many urban planning innovations emerged in response to health crises. The global cholera epidemic in the 1800s led to improved urban sanitation systems. Respiratory infections in overcrowded slums in Europe inspired modern housing regulations during the industrial era.

Urban planning in Africa during colonisation followed a similar pattern. In Anglophone Africa, cholera and bubonic plague outbreaks in Nairobi (Kenya) and Lagos (Nigeria) led to new urban planning strategies. These included slum clearance and urban infrastructure upgrades. Urban planning in French colonial Africa similarly focused on health and hygiene issues, but also safety and security.

Unfortunately regional experiences with cholera, malaria and even Ebola in African cities provide little evidence that they have triggered a new urban planning ethic that prioritises infectious outbreaks. Our recent research paper discusses three areas that can transform urban planning in the continent to prepare for future infectious outbreaks, using lessons from Covid-19.

The Coronavirus and other viruses like Ebola have always been ‘out there’ in nature.

But it’s only when we disrupt the natural habitats of the wild animals. Deadly viruses stay beneath the surface and need just one moment of triggering to emerge in the atmosphere and take the world by storm – historian Dr Mark Honigsbaum. The point is we cannot prevent all spillover events or predict precisely when or where the next one will happen. What we can do — and should do often — is invest in local laboratories and diagnostic services so that we can spot unusual outbreaks early and close them down quickly

We should note that Plasmidium Knowlesi is an example of a form of malaria from monkeys that arose because of urban expansion on forest habitats.

Hyderabad: People sensitised on mosquito breeding

As part of a novel initiative, every Sunday 10 am, 10 minute programme, the entomology wing of Greater Hyderabad Municipal Corporation conducted awareness drive on mosquito breeding grounds at various places on Sunday. They explained the importance of cleanliness and the ways the mosquito breeding takes place in stagnated water. Speaking on the occasion, Banjara Hills Corporator Gadwal Vijayalaxmi called upon everyone not to allow accumulation of water in containers, utensils and surroundings.

Borno, WHO Administer Malaria Prevention Drug on 2.1m Children

WHO National Coordinator Malaria Emergencies in Nigeria, Dr. Iniabasi Nglas gave the figure during a four round Malaria Chemoprevention Campaigns (MPCs aka SMC) in 25 of the 27 local government areas of Borno State. During the advocacy, Nglas said the IDP camps “are given special attention for there is high threat of malaria infection due to the environment. Record has shown that the treatment has reduced malaria morbidity in the state.” She revealed that during the first cycle, 1.9 million children were targeted but due to high reception 2.1 million children were administered with the drug.

Rotary Against Malaria Distributes Nets in PNG

ROTARY Against Malaria has finally completed its distribution of bed net mosquito nets throughout the Eastern Highlands Province (EHP) after three months. Team leader of Rotary Against Malaria in the province, Helmut Magino, during a ceremony in Goroka, acknowledged his working staff, the Eastern Highlands Provincial Health Authority, district health officers, logistic company Mapai Transport, Summer Institute of Linguistics (SIL)
and the communities in Papua New Guinea.

“Without these partners, our work in distributing mosquito nets wouldn’t have been successful,” Mr Magino said. “Mapai Transport assisted with vehicles to travel to the remote parts in Okapa, Henganofi and Lufa. “SIL assisted with distribution via airplane to remote parts which are not connected by road like in Obura-Wonenara district.” The volunteer-run organisation funded by Global Fund, a US-based organisation, distributed 145,900 mosquito nets in the province. “We distributed around 45,000 nets to Okapa and Lufa, 35,000 to Obura-Wonenara and 66,900 to rural areas in Goroka district. “We will visit EHP again next year to distribute nets …”

Donating Emergency IRS Supplies to CHAD

Last week, despite the COVID-19 pandemic, a Hercules military transport aircraft took off from an Israeli military base in the south, filled to capacity with items donated by Israeli Flying Aid IFA and the American Jewish Committee (AJC) — 2,000 six-person tents, personal protection equipment (PPE) for medical teams, backpack sprayers to eradicate malaria-carrying mosquitos, and more.

Why humans can run marathons and apes cannot (implication for plasmodium species)

Chimpanzees share more than 99 percent of their genes with modern humans, but the CMAH gene is one of the areas of difference. Two to three million years ago, gorillas, chimpanzees, and other primates were dying from a type of malaria called Plasmodium reichenowi (Science, 2011;331:540-542). At that time, all primates had a surface protein called Neu5Gc on their cells that was made from Neu5Ac. Then along came a primate with a gene that had lost its ability to make Neu5Gc from Neu5Ac, so it had only Neu5Ac (Proc Natl Acad Sci USA, Sept 6, 2005;102(36):12819-12824).

That pre-human did not die from malaria like other primates, his and her children lived and proliferated, and today their descendants (all humans) have a gene that makes Neu5Ac instead of Neu5Gc. As often happens in nature, the malaria parasite then modified its genetic makeup into a variant called Plasmodium falciparum which can infect humans, but not chimpanzees, so today humans can be infected only with Plasmodium falciparum and chimpanzees can be infected only with Plasmodium reichenowi. This same genetic mutation gave homo sapiens greater endurance so they were able to run long distances while the apes could not, which gave humans an advantage in hunting for food (J Hum Evol, 2014;66:64-82).

Malaria News Today 2020-09-01

Today we feature summaries and abstracts concerning Plasmodium malariae, P. knowlesi and monkey models for vaccine testing, clothianidin insecticide resistance, the mosquito immune system and drug interactions between medicines for malaria patients.

Some mosquitoes already have resistance to the latest weapon against malaria

By Munyaradzi Makoni: An insecticide about to be widely deployed inside African homes to combat malaria-carrying mosquitoes is already losing its punch. Two years ago, the World Health Organization (WHO) gave the green light for clothianidin, long used in agriculture to kill crop pests, to be added to the current mainstays of indoor mosquito control, which are losing their effectiveness as the insects develop resistance. Since then, many African countries have been laying plans to spray the walls of homes with the pesticide—it would represent the first new class of chemicals adopted for such use in decades—and looking anxiously for evidence of pre-existing resistance.

Now, scientists at Cameroon’s Centre for Research in Infectious Diseases (CRID) have found it. They recently sampled mosquitoes from rural and urban areas around Yaoundé, the capital, including two key malaria carriers. In one standard susceptibility assay, exposure to clothianidin for 1 hour killed 100% of Anopheles coluzzii. But in some A. gambiae samples as many as 55% of the mosquitoes survived, the group reported in a preprint posted 7 August on the bioRxiv preprint server.

Atlas of Malaria Mosquitoes’ Immune System Assembled

An international team of scientists led by investigators at the Wellcome Sanger Institute and the NIH has created the first cell atlas of mosquito immune cells to understand how the insects fight malaria, as well as other mosquito-borne infections. The mosquito host is essential for the malaria parasite to complete its lifecycle, so any disruption would dramatically reduce the transmission of one of the world’s deadliest diseases.
Findings from the new study—published recently in Science through an article titled “Mosquito cellular immunity at single-cell resolution“—discussed the discovery of new types of mosquito immune cells, including a rare cell type that could be involved in limiting malaria infection. The authors also identified molecular pathways implicated in controlling the malaria parasite.

Genetic analysis of the orthologous crt and mdr1 genes in Plasmodium malariae from Thailand and Myanmar

Plasmodium malariae is a widely spread but neglected human malaria parasite, which causes chronic infections. The observed polymorphisms in pmcrt and pmmdr1 genes are unlikely to affect protein function and unlikely related to chloroquine drug pressure. Similarly, the absence of pmmdr1 copy number variation suggests limited mefloquine drug pressure on the P. malariae parasite population, despite its long time use in Thailand for the treatment of falciparum malaria.

Quantification of Plasmodium knowlesi versus Plasmodium falciparum in the rhesus liver: implications for malaria vaccine studies in rhesus models

Rhesus macaques are valuable pre-clinical models for malaria vaccine development. The Plasmodium knowlesi/rhesus and Plasmodium falciparum/rhesus models are two established platforms for malaria vaccine testing… Detection of 18S rRNA in the liver following high dose intravenous PfSPZ confirmed that rhesus are modestly susceptible to wild-type P. falciparum sporozoites. However, comparison of 18S rRNA RT-PCR biomarker signal indicates that the P. falciparum liver burden was 3–5 logs lower than in PkSPZ-infected animals. Quantification of this difference in liver stage burden will help guide and interpret data from pre-clinical studies of live-attenuated sporozoite vaccines in rhesus models.

Potential drug–drug interactions associated with adverse clinical outcomes and abnormal laboratory findings in patients with malaria

Hospitalized patients with malaria often present with comorbidities or associated complications for which a variety of drugs are prescribed. Multiple drug therapy often leads to drug–drug interactions (DDIs). The following drug pairs reported the highest frequency of adverse events associated with the interactions; calcium containing products-ceftriaxone, isoniazid–rifampin, pyrazinamide–rifampin, isoniazid–acetaminophen, and ciprofloxacin–metronidazole.

Biology and Malaria Eradication: Are there Barriers?

During a press conference prior to the release of the executive summary of 3-year study of trends and future projections for the factors and determinants that underpin malaria by its Strategic Advisory Group on Malaria Eradication (SAGme), WHO outlined some hopeful signs emanating from the SAGme including

  1. Lack of biological barriers to malaria eradication
  2. Recognition of the massive social and economic benefits that would provide a return on investment in eradication, and
  3. Megatrends in the areas of factors such as land use, climate, migration, urbanization that could inhibit malaria transmission

Concerning the first point, the executive summary notes that, “We did not identify biological or environmental barriers to malaria eradication. In addition, our review of models accounting for a variety of global trends in the human and biophysical environment over the next three decades suggest that the world of the future will have much less malaria to contend with.”

The group did agree that, “using current tools, we will still have 11 million cases of malaria in Africa in 2050.” So one wonders whether there are biological barriers or not.

Interestingly the group did identify, “Potential biological threats to malaria eradication include development of insecticide and antimalarial drug resistance, vector population dynamics and altered vector behaviour. For example, Anopheles vectors might adapt to breeding in polluted water, and mosquito vector species newly introduced to Africa, such as Anopheles stephensi, could spread more widely into urban settings.”

This discussion harkens back to an important conceptual article by Bruce Aylward and colleagues that raised the question in the American Journal of Public Health, “When Is a Disease Eradicable?” They outlined three important criteria that had been proposed at two international conferences in 1997 and 1998.

  1. biological and technical feasibility
  2. costs and benefits, and
  3. societal and political considerations

Their further expansion on the biological issues using smallpox as an example is instructive. They noted that not only are humans essential for the life cycle of the organism, but that there was no other reservoir for the causative virus, and the virus could not amplify in the environment. In short, there were no vectors, as in the case of malaria. The relatively recent documentation of transmission of malaria between humans and other primates of different plasmodium species is another biological concern. At this point, Malaysia, for example, is reporting more cases of Plasmodium knowlesi in humans that either P vivax or P falciparum.

Another biological issue identified by Aylward and colleagues was the fact that smallpox had one effective and proven intervention, the vaccine. Application of the vaccine could be targeted using photograph disease recognition cards as the signs were quite specific to the disease. Malaria has several effective interventions, but most strategies emphasize the importance of using a combination of these, and implementation is met with a number of management and logistical challenges. The signs and symptoms of malaria are confused with a number of febrile illnesses.

Finally, two other issues raised concern. Insecticide resistance was recognized in the first malaria eradication effort, and is raising its head again, as pointed out by SAGme. Comparing smallpox and yaws, the challenge of latent or sub-clinical/asymptomatic infection was mentioned. Malaria too, is beleaguered with this problem.

Clearly, we must not lose momentum in the marathon (not a race) to eliminate malaria, but we must, as WHO stressed at the press conference, increase our research and development efforts to strengthen existing tools and develop new once to address the biological and logistical challenges.

The Monkey on the Back of Malaria Elimination

Concerning malaria elimination, “WHO grants this certification when a country has proven, beyond reasonable doubt, that the chain of local transmission of all human (emphasis added) malaria parasites has been interrupted nationwide for at least the past 3 consecutive years.” This target is challenging enough, but becomes more complicated when we consider that zoonotic transmission of malaria among monkeys and humans has been documented in Brazil and Southeast Asia. We cannot expect monkeys to sleep under bednets, so creative and realistic solutions are needed.

The Malaria Eradication Research Agenda (malERA) recognizes this problem. Plasmodium knowlesi, originally found in macaque monkeys in Southeast Asia has been dubbed the fifth human malaria due to its spread to people as deforestation has disturbed the habitat of the monkeys. In particular malERA addresses the challenge of understanding the upward trend of this malaria infection in that region and the need for better understanding of transmission dynamics and proper diagnosis.

The danger of P. knowlesi is heightened by difficulties in diagnosing it and distinguishing it from other malaria species. “Recently, the prevalence of human infection with a simian malaria parasite, P. knowlesi, has become an important issue in a wide area of Southeast Asia. The identification of this parasite by microscopy is very difficult because it resembles the P. malariae parasite. However, the symptoms caused by P. malariae and P. knowlesi are very different, with only P. knowlesi causing severe and life-threatening malaria” (Komaki-Yasuda et al.)

Reports from Brazil highlight another ‘simian hotspot.’ While P. Knowlesi represents monkey infections reaching humans, the opposite may have happened to establish a reservoir in the New World. “P. vivax lineages appearing to originate from Melanesia that were putatively carried by the Australasian peoples who contributed genes to Native Americans. Importantly, mitochondrial lineages of the P. vivax-like species P. simium are shared by platyrrhine monkeys and humans in the Atlantic Forest ecosystem, but not across the Amazon, which most likely resulted from one or a few recent human-to-monkey transfers.”  But looking even further back in natural history, Escalante and colleagues found, “compelling evidence that P. vivax is derived from a species that inhabited macaques in Southeast Asia.”

A recent study in this area found the worrying results that, “The low incidence of cases and the low frequency of asymptomatic malaria carriers investigated make it unlikely that the transmission chain in the region is based solely on human hosts, as cases are isolated one from another by hundreds of kilometers and frequently by long periods of time, reinforcing instead the hypothesis of zoonotic transmission.”

In Africa, Linda Duval and co-researchers, who found P. falciparum in blood samples from two chimpanzees belonging to two different subspecies, warn that, “If malignant malaria were eradicated from human populations, chimpanzees, in addition to gorillas, might serve as a reservoir for P. falciparum,”

It appears that the dynamics between monkeys, malaria and humans has a long history. Even once certified malaria-free countries face the threat of imported malaria from people crossing borders. Now we must recognize that the threat may already live within borders. So since existing malaria interventions to protect humans from malaria cannot be applied to monkeys, accelerated research on the genetics of the parasite and the mosquito is needed to prevent both primate groups from getting malaria.