Today we share news and abstracts concerning detecting malaria in pregnancy, news about the opening remarks from the WHO Director General at a special malaria and COVID-19 webinar, resumption of NTD activities after COVID-19 restrictions reduced, and mapping of Ebola carrying bats whose territory overlaps malaria in Africa. Click on the links to read more.
Prevalence and clinical impact of malaria infections detected with a highly sensitive HRP2 rapid diagnostic test in Beninese pregnant women
While sub-microscopic malarial infections are frequent and potentially deleterious during pregnancy, routine molecular detection is still not feasible. This study aimed to assess the performance of a Histidine Rich Protein 2 (HRP2)-based ultrasensitive rapid diagnostic test (uRDT, Alere Malaria Ag Pf) for the detection of infections of low parasite density in pregnant women.
This study demonstrates the higher performance of uRDT, as compared to cRDTs, to detect low parasite density P. falciparum infections during pregnancy, particularly in the 1st trimester. uRDT allowed the detection of infections associated with maternal anaemia.
The distribution range of Ebola virus carriers in Africa may be larger than previously assumed
Since Ebola overlaps both symptomatically and geographically with malaria in Africa, it is “Worrying that science has hitherto underestimated the range of Ebola-transmitting bat and fruit bat species. In this case, the models would provide a more realistic picture,” explains Dr. Lisa Koch
Based on ecological niche modeling, his team was able to show that the respective bat and fruit bat species are able to thrive in West and East Africa, including large parts of Central Africa. A wide belt of potential habitats extends from Guinea, Sierra Leone, and Liberia in the west across the Central African Republic, the Republic of the Congo and the Democratic Republic of the Congo to Sudan and Uganda in the East. A few of the studied bats and fruit bats may even occur in the eastern part of South Africa.
WHO Director-General’s Opening Remarks At the Webinar – Responding to the Double Challenge of Malaria and Covid-19
The WHO Director General is encouraged by efforts to maintain malaria services despite the COVID-19 outbreak, but says, “I would like to recognize and applaud all these efforts, and to thank all of you who have worked so hard to preserve and maintain those services to the greatest degree possible. However, despite these actions, it breaks my heart to report that we still expect to see an increase in cases and deaths from malaria.
“In a recent WHO survey of 105 countries, 46% of countries reported disruptions in malaria diagnosis and treatment. These disruptions threaten to set us back even further in realizing our shared vision for a malaria-free world.”
NTD Disease treatments restart in Africa as COVID-19 restrictions ease
It is not just malaria services that have been disrupted by COVID-19 responses. Treatment programmes that will reach millions of Africans at risk from debilitating neglected tropical diseases (NTDs) have restarted in a significant step towards COVID-19 recovery. Around one million people in Jigawa state, Nigeria have received antibiotics to treat the blinding eye disease trachoma and stop it from spreading.
Nigeria is the first country that Sightsavers and partners has supported to resume work on NTDs, which can have a devastating impact on some of the poorest communities in the world, with other African countries due to follow soon. In April, the threat of COVID-19 led the World Health Organization to recommend suspending mass treatment campaigns, which treat and prevent these diseases, but it has since provided guidance on restarting activities safely.
Much attention is focused on the broader environmental and climatic consequences of deforestation, especially as this has seemed to pick up pace in places like the Amazon Basin. More attention is also needed concerning the disease transmission implications of deforestation. Recent studies have shed light on the problem. Basically deforestation as a result of urbanization or expanding commercial agriculture and related human activity brings people closer to areas where diseases can spread.
The connection between bats and the spread of Ebola in humans has been posited for some time. Forest News notes that “Fruit bats (Pteropodidae) are suspected reservoir hosts for the Ebola virus,” and thus, “Deforestation may accelerate the spread of the deadly Ebola disease in the rainforests of West and Central Africa by increasing human-bat interactions.” They are sharing information by Olivero and colleagues recently published in Mammal Review.
These researchers “show that the range of some fruit bat species is linked to human activities within the favourable areas for the Ebola virus. More specifically, the areas where human activities favour the presence of five fruit bat species overlap with the areas where EVD outbreaks in humans were themselves favoured by deforestation.” They have modeled and mapped an area in West and Central Africa based on climate, including annual temperature ranges, the presence of rainforest and mammal distribution to create an area known as “The Ebola Virus Area.”
Concerning malaria, research by Chua and colleagues in Malaysia found that, “contributes to a growing body of evidence implicating environmental changes due to deforestation, expansion of agricultural and farming areas, and development of human settlements near to forest fringes in the emergence of P. knowlesi in Sabah.” Their research is part of more than a dozen studies over the past nine years that links deforestation and greater interaction between humans and macaque monkeys, the normal victim of P. knowlesi. One of the earlier studies reports that, ” ongoing ecological changes resulting from deforestation, with an associated increase in the human population, could enable this pathogenic species of Plasmodium to switch to humans as the preferred host.”
Eliminating the mammal hosts of these diseases is not an option because as Olivero explained about bats, “The entire function and ecology of forests would be put at risk if these vital pollinators and seed dispersers are eliminated.”
Considering another tropical disease, Visser warns that, “Climate change, deforestation, urbanization, and increased population mobility have made the risk of large outbreaks of yellow fever more likely than ever.” The lesson from these experiences is not mainly that we need to increase coverage of proven preventive measures, but that we need broader change in our approaches and policies toward land use.
Below we highlight some of the news we have shared on our Facebook Tropical Health Group page during the past week.
If all it took to eradicate a disease was a well proven drug, vaccine or technology, we would not be still reporting on polio, measles and guinea worm, to name a few. In the past week Afghanistan reported 2 wild poliovirus type 1 (WPV1) cases, and Pakistan had 3 WPV1 cases. Circulating vaccine-derived poliovirus type 2 (cVDPV2) was reported in Nigeria (1), DRC (4) and Ethiopia (3) from healthy community contacts.
Continued Ebola Challenges
In the seven days from Saturday to Friday (June 28) there were 71 newly confirmed Ebola Cases and 56 deaths reported by the Democratic Republic of Congo’s Ministry of Health. As Ebola cases continue to pile up in the Democratic Republic of the Congo (DRC), with 12 more confirmed Thursday and 7 more Friday, a USAID official said four major donors have jump-started a new strategic plan for coordinating response efforts. To underscore the heavy toll the outbreak has caused, among its 2,284 cases, as noted on the World Health Organization Ebola dashboard today, are 125 infected healthcare workers, including 2 new ones, DRC officials said.
Pacific Standard explained the differences in Ebola outbreaks between DRC today and the West Africa outbreak of 2014-16. On the positive side are new drugs used in organized trials for the current outbreak. The most important factor is safe, effective vaccine that has been tested in 2014-16, but is now a standard intervention in the DRC. While both Liberia and Sierra Leone had health systems and political weaknesses as post-conflict countries, DRC’s North Kivu and Ituri provinces are currently a war zone, effectively so for the past generation. Ebola treatment centers and response teams are being attacked. There are even cultural complications, a refusal to believe that Ebola exists. So even with widespread availability of improved technologies, teams may not be able to reach those in need.
To further complicate matters in the DRC, Doctors Without Borders (MSF) “highlighted ‘unprecedented’ multiple crises in the outbreak region in northeastern DRC. Ebola is coursing through a region that is also seeing the forced migration of thousands of people fleeing regional violence and is dealing with another epidemic. Moussa Ousman, MSF head of mission in the DRC, said, ‘This time we are seeing not only mass displacement due to violence but also a rapidly spreading measles outbreak and an Ebola epidemic that shows no signs of slowing down, all at the same time.’”
NIPAH and Bats
Like Ebola, NIPAH is zoonotic, and also involves bats, but the viruses differ. CDC explains that, “Nipah virus (NiV) is a member of the family Paramyxoviridae, genus Henipavirus. NiV was initially isolated and identified in 1999 during an outbreak of encephalitis and respiratory illness among pig farmers and people with close contact with pigs in Malaysia and Singapore. Its name originated from Sungai Nipah, a village in the Malaysian Peninsula where pig farmers became ill with encephalitis.
A recent human outbreak in southern India has been followed up with a study of local bats. In a report shared by ProMED, out of 36 Pteropus species bats tested for Nipah, 12 (33%) were found to be positive for anti-Nipah bat IgG antibodies. Unlike Ebola there are currently no experimental drugs or vaccines.
Climate Change and Dengue
Climate change is expected to heighten the threat of many neglected tropical diseases, especially arboviral infections. For example, the New York Times reports that increases in the geographical spread of dengue fever. Annually “there are 100 million cases of dengue infections severe enough to cause symptoms, which may include fever, debilitating joint pain and internal bleeding,” and an estimated 10,000 deaths. Dengue is transmitted by Aedes mosquitoes that also spread Zika and chikungunya. A study, published Monday in the journal Nature Microbiology, found that in a warming world there is a strong likelihood for significant expansion of dengue in the southeastern United States, coastal areas of China and Japan, as well as to inland regions of Australia. “Globally, the study estimated that more than two billion additional people could be at risk for dengue in 2080 compared with 2015 under a warming scenario.”
Schistosomiasis – MDA Is Not Enough, and Neither Are Supplementary Interventions
Schistosomiasis is one of the five neglected tropical diseases (NTDs) that are being controlled and potentially eliminated through mass drug administration (MDA) of preventive chemotherapy (PCT), in this case praziquantel. In The Lancet Knopp et al. reported that biannual MDA substantially reduced Schistosomiasis haematobium prevalence and infection intensity but was insufficient to interrupt transmission in Zanzibar. In addition, neither supplementary snail control or behaviour change activities did not significantly boost the effect of MDA. Most MDA programs focus on school aged children, and so other groups in the community who have regular water contact would not be reached. Water and sanitation activities also have limitations. This raises the question about whether control is acceptable for public health, or if there needs to be a broader intervention to reach elimination?
Trachoma on the Way to Elimination
Speaking of elimination, WHO has announced major “sustained progress” on trachoma efforts. “The number of people at risk of trachoma – the world’s leading infectious cause of blindness – has fallen from 1.5 billion in 2002 to just over 142 million in 2019, a reduction of 91%.” Trachoma is another NTD that uses the MDA strategy.
The news about NTDs from Dengue to Schistosomiasis to Trachoma is complicated and demonstrates that putting diseases together in a category does not result in an easy choice of strategies. Do we control or eliminate or simply manage illness? Can our health systems handle the needs for disease elimination? Is the public ready to get on board?
And concerning being complicated, malaria this week again shows many facets of challenges ranging from how to recognize and deal with asymptomatic infection to preventing reintroduction of the disease once elimination has been achieved. Several reports this week showed the particular needs for malaria intervention ranging from high burden areas to low transmission verging on elimination to preventing re-introduction in areas declared free from the disease.
In South West, Nigeria Dokunmu et al. studied 535 individuals aged from 6 months were screened during the epidemiological survey evaluating asymptomatic transmission. Parasite prevalence was determined by histidine-rich protein II rapid detection kit (RDT) in healthy individuals. They found that, “malaria parasites were detected by RDT in 204 (38.1%) individuals. Asymptomatic infection was detected in 117 (57.3%) and symptomatic malaria confirmed in 87 individuals (42.6%).
Overall, detectable malaria by RDT was significantly higher in individuals with symptoms (87 of 197/44.2%), than asymptomatic persons (117 of 338/34.6%)., p = 0.02. In a sub-set of 75 isolates, 18(24%) and 14 (18.6%) individuals had Pfmdr1 86Y and 1246Y mutations. Presence of mutations on Pfmdr1 did not differ by group. It would be useful for future study to look at the effect of interventions such as bednet coverage. While Southwest Nigeria is a high burden area, the problem of asymptomatic malaria will become an even bigger challenge as prevalence reduces and elimination is in sight.
Sri Lanka provides a completely different challenge from high burden areas. There has been no local transmission of malaria in Sri Lanka for 6 years following elimination of the disease in 2012. Karunasena et al. report the first case of introduced vivax malaria in the country by diagnosing malaria based on microscopy and rapid diagnostic tests. “The imported vivax malaria case was detected in a foreign migrant followed by a Plasmodium vivax infection in a Sri Lankan national who visited the residence of the former. The link between the two cases was established by tracing the occurrence of events and by demonstrating genetic identity between the parasite isolates. Effective surveillance was conducted, and a prompt response was mounted by the Anti Malaria Campaign. No further transmission occurred as a result.”
Bangladesh has few but focused areas of malaria transmission and hopes to achieve elimination of local transmission by 2030. A particular group for targeting interventions is the population of slash and burn cultivators in the Rangamati District. Respondents in this area had general knowledge about malaria transmission and modes of prevention and treatment was good according to Saha and the other authors. “However, there were some gaps regarding knowledge about specific aspects of malaria transmission and in particular about the increased risk associated with their occupation. Despite a much-reduced incidence of malaria in the study area, the respondents perceived the disease as life-threatening and knew that it needs rapid attention from a health worker. Moreover, the specific services offered by the local community health workers for malaria diagnosis and treatment were highly appreciated. Finally, the use of insecticide-treated mosquito nets (ITN) was considered as important and this intervention was uniformly stated as the main malaria prevention method.”
Kenya offers some lessons about low transmission areas but also areas where transmission may increase due to climate change. A matched case–control study undertaken in the Western Kenya highlands. Essendi et al. recruited clinical malaria cases from health facilities and matched to asymptomatic individuals from the community who served as controls in order to identify epidemiological risk factors for clinical malaria infection in the highlands of Western Kenya.
“A greater percentage of people in the control group without malaria (64.6%) used insecticide-treated bed nets (ITNs) compared to the families of malaria cases (48.3%). Low income was the most important factor associated with higher malaria infections (adj. OR 4.70). Houses with open eaves was an important malaria risk factor (adj OR 1.72).” Other socio-demographic factors were examined. The authors stress the need to use local malaria epidemiology to more effectively targeted use of malaria control measures.
The key lesson arising from the forgoing studies and news is that disease control needs strong global partnerships but also local community investment and adaptation of strategies to community characteristics and culture.
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.
On World Population Day (July 11) one often thinks of family planning. A wider view was proposed by resolution 45/216 of December 1990, of the United Nations General Assembly which encouraged observance of “World Population Day to enhance awareness of population issues, including their relations to the environment and development.”
A relationship still exists between family planning and malaria via preventing pregnancies in malaria endemic areas where the disease leads to anemia, death, low birth weight and stillbirth. Other population issues such as migration/mobility, border movement, and conflict/displacement influence exposure of populations to malaria, NTDs and their risks. Environmental concerns such as land/forest degradation, occupational exposure, population expansion (even into areas where populations of monkeys, bats or other sources of zoonotic disease transmission live), and climate warming in areas without prior malaria transmission expose more populations to mosquitoes and malaria.
Ultimately the goal of eliminating malaria needs a population based focus. The recent WHO malaria elimination strategic guidance encourages examination of factors in defined population units that influence transmission or control.
Today public health advocates are using the term population health more. The University of Wisconsin Department of Population Health Sciences in its blog explained that “Population health is defined as the health outcomes of a group of individuals, including the distribution of such outcomes within the group.” World Population Day is a good time to consider how the transmission or prevention of malaria, or even neglected tropical diseases, is distributed in our countries, and which groups and communities within that population are most vulnerable.
World Population Day has room to consider many issues related to the health of populations whether it be reproductive health, communicable diseases or chronic diseases as well as the services to address these concerns.
The Earth Day website notes that, “Our planet is currently losing over 15 billion trees each year—that’s 56 acres of forest every minute. We’re working hard to reverse that trend by supporting global reforestation projects. Earth Day Network’s Reforestation Campaign benefits local communities, increases habitat for species, and combats climate change.”
This habitat change if often conducive to the spread of malaria in areas and among populations that may not have been affected before. Specifically, “More risks associated with El Niño are: flooding and landslides in the Americas, drought in Southeast Asia and Australia, scrambled fisheries, and malaria, cholera, and dengue outbreaks.”
Terry Devitt reported that the incidence of malaria jumps when Amazon forests are cut, establishing a firm link between environmental change and human disease. The report, which combines detailed information on the incidence of malaria in 54 Brazilian health districts and high-resolution satellite imagery of the extent of logging in the Amazon forest, shows that clearing tropical forest landscapes boosts the incidence of malaria by nearly 50 percent (according to Olson and colleagues).
Moyes et al. Predicted the geographical distributions of the macaque hosts and mosquito vectors of Plasmodium knowlesi malaria in forested and non-forested areas of Southeast Asia. When urbanization and deforestation bring people into habitats they never lived in, zoonotic transmission of malaria results. Fornace et al. similarly observed that, “Marked spatial heterogeneity in P. knowlesi incidence was observed, and village-level numbers of P. knowlesi cases were positively associated with forest cover and historical forest loss in surrounding areas. These results suggest the likelihood that deforestation and associated environmental changes are key drivers in P. knowlesi transmission in these areas” of Malaysia.
Back to Brazil, de Alvarenga and co-researchers reported in the transmission of Plasmodium simian malaria in the Brazilian Atlantic forest as a natural infection of capuchin monkeys (Cebinae subfamily). Because of human movement into forest areas, cases among people have now been documented.
The zoonotic transmission of malaria to humans due to changes in climate, environment and habitat pose another unwanted challenge to global efforts to eliminate malaria. On Earth Day it is imperative for malaria control and elimination workers to collaborate closely with colleagues in environmental health and protection.