Tropical Health Matters

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).

Today, we are sharing more updates from newsletters and journal abstracts found online. Issues include citizens in Rwanda trapping mosquitoes, the need for standardizing microscopy, more information on Uganda’s Malaria fund, the challenge of containing three epidemics at once, an increase in cases in Namibia and genetic diversity of the parasite in Comoros. Click on links to read details.

Citizen science shows great potential to reduce malaria burden

A year-long collection of mosquitoes with self-made traps and over a hundred volunteers in rural Rwanda reporting levels of mosquito nuisance revealed when and where malaria risks were the highest. In addition to their reporting, the volunteers appeared to distribute knowledge and skills on controlling malaria within communities. Studies by Wageningen University & Research and the University of Rwanda show that citizen science has great potential to reduce the disease burden across the globe.

Uganda renews fight to eliminate malaria by 2030 – more on Malaria Free Uganda Fund

Uganda says it is fast-tracking efforts to eliminate malaria, which continues to take lives and bleed the country’s economy more than any other disease. The disease is responsible for 30 to 40 percent of outpatient hospital visits, 15 to 20 percent of admissions, and 10 percent of inpatient deaths, mostly pregnant mothers and children, according to the health ministry figures. The country on September 2 launched the board of directors of the Malaria Free Uganda Fund as part of its continued investment to eliminate the disease by 2030, as per the global target.

Malaria Free Uganda Fund is a nonprofit public-private partnership established to mainstream responsibility for malaria across all sectors and help remove financial and operational bottlenecks in fighting the disease. The National Malaria Control Program currently faces a three-year 206 U.S. million dollars budget gap, or 33 percent of the total, according to the ministry of health.  External donors, according to the ministry, fund over 95 percent of the fight against the disease in the country. The country is now looking at domestic resourcing in view of the global uncertainties like the COVID-19 pandemic that is affecting foreign financing. “The talent and experience we have mobilized to this board from the private and civil society will help the government achieve a significant reduction of malaria cases and deaths in Uganda,” said Ruth Aceng, minister of health while launching the board here.

Namibia records 12,507 malaria cases, 40 deaths in 2020

Namibia’s malaria cases this year increased to 12,507 from 2,841 recorded in 2019, according to statistics from the Ministry of Health. The southern African country recorded 31,000 cases of malaria in 2018. The National Vector-borne Diseases Control Program from the Health Ministry which monitors the weekly malaria situation in the country shows that this year alone 12,507 malaria cases where recorded, while 40 deaths occurred.

The ministry said the huge difference between 2019 and this year is attributed to the fact that 2019, was a drought year and the rainfall pattern was not similar to 2020 and 2018, hence the decline in malaria cases happened in 2019. According to the ministry, currently the implementation of the program activities amid COVID-19 is on halt due to some bottlenecks.

Congo sees increase in plague, at least 10 deaths this year

DR Congo is seeing an upsurge in cases of the plague, as the vast Central African nation also battles outbreaks of COVID-19 and Ebola. Since June, Congo has recorded at least 65 cases of the plague, including at least 10 deaths, in the eastern Ituri province according to Ituri provincial chief of health Dr. Louis Tsolu. While the plague is endemic in Ituri province, the number of cases is increasing and has already surpassed the total recorded in 2019 which had 48 cases and eight deaths, according to WHO.

Towards harmonization of microscopy methods for malaria clinical research studies

Microscopy performed on stained films of peripheral blood for detection, identification and quantification of malaria parasites is an essential reference standard for clinical trials of drugs, vaccines and diagnostic tests for malaria. The value of data from such research is greatly enhanced if this reference standard is consistent across time and geography. Adherence to common standards and practices is a prerequisite to achieve this. The rationale for proposed research standards and procedures for the preparation, staining and microscopic examination of blood films for malaria parasites is presented here with the aim of improving the consistency and reliability of malaria microscopy performed in such studies.

These standards constitute the core of a quality management system for clinical research studies employing microscopy as a reference standard. They can be used as the basis for the design of training and proficiency testing programmes as well as for procedures and quality assurance of malaria microscopy in clinical research.

Genetic diversity of Plasmodium falciparum in Grande Comore Island

Despite several control interventions resulting in a considerable decrease in malaria prevalence in the Union of the Comoros, the disease remains a public health problem with high transmission in Grande Comore compared to neighbouring islands. In this country, only a few studies investigating the genetic diversity of Plasmodium falciparum have been performed so far. For this reason, this study aims to examine the genetic diversity of P. falciparum by studying samples collected in Grande Comore in 2012 and 2013, using merozoite surface protein 1 (msp1), merozoite surface protein 2 (msp2) and single nucleotide polymorphism (SNP) genetic markers.

Various updates were found in newsletters and journal abstracts online today. These looked at mosquitoes – what attracts them to people, how ookinetes move in the midgut, and how perlite from volcanic rock may be a barrier repellent. Nigeria reports that there is no ACT resistance – so far.  And malaria partners join to coordinate actions in Uganda.  Click on links to read details.

Nigeria yet to detect resistance of malaria parasite to ACTs, says ministe

Contrary to reports that Africa has for the first time identified resistance strain of the malaria parasite to the drug of choice, Artemisinin Combination Therapy (ACT), the Minister of Health, Dr. Osagie Emmanuel Ehanire, on Monday said a study conducted in three states of the country showed there is no such phenomenon in Nigeria.  “However, we are still monitoring the situation. We insist that people should conduct a malaria test before using the drug of choice. This we hope will help prevent any kind of resistance of the malaria parasite to ACTs.”

Ministry of Health launches the Malaria Free Uganda Fund

Health Minister Dr Jane Ruth Aceng told journalists in Kampala today that the idea of having this new board was reached after realizing that different entities have been conducting the same malaria control related work. She said that the ministry resolved that mainstreaming responsibility will remove financial and operational bottlenecks that deter them from achieving set targets for elimination of the disease. The fund with a board of 11 members is chaired by Kenneth Wycliffe Mugisha of the Rotarian Malaria Partners-Uganda.

Volcanic Rock Yields a New Kind of Insecticide for Mosquitoes

Insecticide resistance to pesticides has become widespread in mosquito populations, making insecticides less effective over time. Therefore, there is an urgent need for insecticides with alternative modes of action. tested a material derived from volcanic rock, perlite, as a potential non-chemical insecticide against Anopheles gambiae, one of the primary mosquitoes that spreads malaria in Africa. In their new report published in August in the Journal of Medical Entomology, they show that perlite has encouraging potential as a mechanical insecticide. Perlite is believed to act by causing dehydration in the mosquitoes. read more…

Mosquitoes love pregnant, beer-drinking exercisers with Type O blood

Mosquitoes spread Zika, West Nile, Chikungunya, Dengue, and Malaria, resulting in 700 million illnesses a year and a million deaths. Even if you don’t get sick from a mosquito bite, the blood thinner they pump into your flesh before draining your blood causes swelling and itching. This article in Smithsonian Magazine lists the factors that make some people more tempting targets than others to mosquito bites. They include:

• Blood type: “One study found that in a controlled setting, mosquitoes landed on people with Type O blood nearly twice as often as those with Type A.”
• Carbon Dioxide: “people who simply exhale more of the gas over time—generally, larger people—have been shown to attract more mosquitoes than others.”
• Exercise: “mosquitoes find victims at closer range by smelling the lactic acid, uric acid, ammonia and other substances expelled via their sweat”
• Skin bacteria: “scientists found that having large amounts of a few types of bacteria made skin more appealing to mosquitoes”
• Beer: “Just a single 12-ounce bottle of beer can make you more attractive to the insects”
• Pregnancy: “pregnant people exhale about 21 percent more carbon dioxide and are on average about 1.26 degrees Fahrenheit warmer than others”
• Clothing color: “wearing colors that stand out (black, dark blue or red) may make you easier to find”
• Genetics: “underlying genetic factors are estimated to account for 85 percent of the variability between people in their attractiveness to mosquitoes”

Live In Vivo Imaging of Plasmodium Invasion of the Mosquito Midgut

Malaria is one of the most devastating parasitic diseases in humans and is transmitted by anopheline mosquitoes. The mosquito midgut is a critical barrier that Plasmodium parasites must overcome to complete their developmental cycle and be transmitted to a new host. Here, we developed a new strategy to visualize Plasmodium ookinetes as they traverse the mosquito midgut and to follow the response of damaged epithelial cells by imaging live mosquitoes. Understanding the spatial and temporal aspects of these interactions is critical when developing novel strategies to disrupt disease transmission.

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.

Botswana is one of a handful of countries in Southern Africa that are nearing malaria elimination targets. The information below is extracted from WHO’s Elimination 2020 program site and shared verbatim.

“Botswana has made impressive progress in reducing indigenous malaria transmission, from a reported 71 000 cases in 2000 to 533 in 2018. Despite significant variation from year to year – with a higher number of malaria cases in 2014, 2016 and 2017 – the country has continued to report an overall decline in both cases and deaths since 2000.

“Challenges faced by Botswana’s national malaria control programme include the perception, in some communities, that malaria is a low priority disease, which can lead to people not protecting themselves with insecticide-treated nets and other WHO-recommended prevention measures. Added to this, some residents do not accept vector control activities such as insecticide spraying inside homes. However, the government’s commitment to eliminate malaria remains strong.

“WHO lists the following Successes in Botswana and the accompanying graph confirms the overall drop, despite some increases:

• 69% decrease in number of reported malaria cases following outbreaks in 2014, 2016 and 2017;
• all districts using District Health Information Software 2 (DHIS2) for real-time malaria reporting
• mapping of all malaria cases at household level and stratification at village level
• adoption of the Community Acting Together to Eliminate Malaria (CATTEM) approach
  enhanced community monitoring in malarious districts by malaria surveillance agents”

Hopefully with geographical and epidemiological targeting and attention to early warnings about climate change, Botswana can be among the next group of countries achieving malaria elimination.

In the past week more attention was drawn to the apparently never-ending year-long Ebola outbreak in the northeast of the Democratic Republic of the Congo. Regarding other diseases, there is new information on the RTS,S malaria vaccine, river prawns have been found to play a biological control role in schistosomiasis, and an update from the World Health Organization on essential medicines and diagnostics. New malaria vector control technologies are discussed.

Second Largest Ebola Outbreak One Year On

Ronald A. Klain and Daniel Lucey in the Washington Post observed raised concern that, “the disease has since crossed one border (into Uganda) and continues to spread. In the absence of a trajectory toward extinguishing the outbreak, the opposite path — severe escalation — remains possible. The risk of the disease moving into nearby Goma, Congo — a city of 1 million residents with an international airport.”

They added their voices to a growing number of experts who are watching this second biggest Ebola outbreak in history and note that, “As the case count approaches 2,500 with no end in sight, it is time for the WHO to declare the outbreak a public health emergency of international concern — a ‘PHEIC’ — to raise the level of global alarm and signal to nations, particularly the United States, that they must ramp up their response.” They call for three actions: 1) improved security for health workers in the region, 2) stepped up community engagement and 3) extended health care beyond Ebola treatment. The inability to adequately respond to malaria, diarrheal diseases and maternal health not only threated life directly, but also threated community trust, putting health workers’ lives at risk.

Olivia Acland, a freelance journalist based in DRC, reporting for the New Humanitarian describes the insecurity and the recent “wave of militia attacks in the Democratic Republic of Congo’s northeastern Ituri province has left hundreds dead and roughly 300,000 displaced in recent weeks, triggering a new humanitarian crisis in a region.” Specifically, “Ituri, a fertile region rich in gold deposits, has been an epicentre of conflict in Congo for decades. Between 1999 and 2003, around 60,000 people were killed here, as a power struggle between rebel groups escalated into ethnic violence,” related to traditional tensions between Hema cattle herders and Lendu farmers with roots in Belgian colonization.

Updates from the DRC Ministry of Health report on average 11 new Ebola cases per day in the past week. So far over 160,000 people have been vaccinated, and yet the spread continues. The Ministry also describes new protocol contains three vaccinations strategies that can be used depending on the environment in which confirmed cases are found including:

• Classic Ring: The classic strategy of vaccinating contacts of confirmed cases and contact contacts.
• Enlarged ring: It is also possible to vaccinate all inhabitants of houses within 5 meters around the outbreak of a confirmed case.
• Geographical Ring: In an area where team safety can not be guaranteed, they can vaccinate an entire village or neighborhood.

Malaria Vaccines, Essential Drugs and New Vector Control Technologies

Halidou Tinto and colleagues enrolled two age groups of children in a 3-year extension of the RTS,S/AS01 vaccine efficacy trial: 1739 older children (aged 5–7 years) and 1345 younger children (aged 3–5 years). During extension, they reported 66 severe malaria cases. Overall they found that, “severe malaria incidence was low in all groups, with no evidence of rebound in RTS,S/AS01 recipients, despite an increased incidence of clinical malaria in older children who received RTS,S/AS01 compared with the comparator group in Nanoro. No safety signal was identified,” as seen in The Lancet.

WHO has updated the global guidance on medicines and diagnostic tests to address health challenges, prioritize highly effective therapeutics, and improve affordable access. Section 6.5.3 presents antimalarial medicines including curative treatment (14 medicines) for both vivax and falciparum and including tablets and injectables. Prophylaxis includes 6 medicines including those for IPTp and SMC. The latest guidance can be downloaded at WHO.

Paul Krezanoski reports on a new technology to monitor bednet use and tried it out in Ugandan households. As a result. “Remote bednet use monitors can provide novel insights into how bednets are used in practice, helping identify both households at risk of malaria due to poor adherence and also potentially novel targets for improving malaria prevention.

In another novel technological approach to vector control, Humphrey Mazigo and co-researchers tested malaria mosquito control in rice paddy farms using biolarvicide mixed with fertilizer in Tanzanian semi-field experiments. The intervention sections (with biolarvicide) had lowest mean mosquito larvae abundance compared to control block and did not affect the rice production/harvest.

Prawns to the Rescue in Senegal Fighting Schistosomiasis and Poverty

Anne Gulland reported how Christopher M. Hoover et al. discovered how prawns could be the key to fighting poverty and schistosomiasis, a debilitating tropical disease. They found that farming the African river prawn could fight the disease and improve the lives of local people, because the African river prawn is a ‘voracious’ predator of the freshwater snail, which is a carrier of schistosomiasis.

The researchers in Senegal said that, “market analysis in Senegal had shown there was significant interest among restaurant owners and farmers in introducing prawns to the diet.” The prawn could also for the basis of aquaculture in rice paddies and remove the threat of schistosomiasis from the rice workers.

—- Thank you for reading this week’s summary. These weekly abstractings have replaced our occasional mailings on tropical health issues due to fees introduced by those maintaining the listserve website. Also continue to check the Tropical Health Twitter feed, which you can see running on this page.

This week started with articles that drew attention to the challenges of malaria in low transmission areas and with low density infections. Malaria Journal has provided several insightful articles toward this end.

Being an island has certainly helped Zanzibar make progress toward malaria elimination as witness the fact that malaria prevalence has remained below 1% for the past decade. Not only does Zanzibar still face threats of infection from the mainland, it may also experience an upsurge locally if residual transmission and the role of human behavior and community actions are not well understood. April Monroe et al. conducted in-depth interviews with community members and local leaders across six sites on Unguja, Zanzibar as well as semi-structured community observations of night-time activities and special events to learn more.

While there was high reported ITN use, there were also times when people were exposed t mosquitoes while being outdoors during biting times. This could be around the house, or at special night events like such as weddings, funerals, and religious ceremonies. Men spent more time outdoors than women. Clearly appropriate interventions and needed and should be promoted in culturally appropriate ways in order to further reduce and eventually eliminate transmission.

Angela Early and colleagues presented findings on a diagnostic process of deep sequencing for understanding the dynamics and complexity of Plasmodium infections, but stress that knowing the lower limit of detection is challenging. They present “a new amplicon analysis tool, the Parallel Amplicon Sequencing Error Correction (PASEC) pipeline, is used to evaluate the performance of amplicon sequencing on low-density Plasmodium DNA samples.”

The authors learned that, “four state-of-the-art tools resolved known haplotype mixtures with similar sensitivity and precision.” They also cautioned that, “Samples with very low parasitemia and very low read count have higher false positive rates and call for read count thresholds that are higher than current default recommendations.” Better understanding of the genetic mix of plasmodium infections as countries move toward low transmission and elimination is crucial for selecting appropriate interventions and evaluating their outcomes.

Hannah Edwards and co-researchers examined conditions for malaria transmission along the Thailand-Myanmar border in areas approaching malaria elimination. While prevalence may be less than 1%, residual transmission still occurs. Transmission occurs not only around residences but in the forests where people work. The researchers therefore looked at the behavior of both humans and insects. Overall, they found that, “Community members frequently stayed overnight at subsistence farm huts or in the forest. Entomological collections showed higher biting rates of primary vectors in forested farm hut sites and in a more forested village setting compared to a village with clustered housing and better infrastructure.”

While mosquitoes preferred to bite inside huts, their threat was magnified by those who did not use long lasting insecticide-treated nets (LLINs). While out in the farms and forests, people tended to wake early and increase their likelihood of being bitten. The authors discuss the challenges of dual residences in terms of LLIN ownership and even concerning the potential access to indoor residual spraying. The definition for universal net coverage needs to expand from one net per two people to include adequate nets wherever people are located.

The Amazonian area of Brazil is another area working toward malaria elimination, in particular, Plasmodium vivax. Felipe Leão Gomes Murta et al. also looked at the human side of the equation and identified misperceptions by both community members and health workers that could inhibit elimination efforts. They found, “many myths regarding malaria transmission and treatment that may hinder the sensitization of the population of this region in relation to the use of current control tools and elimination strategies, such as mass drug administration (MDA),” and LLINs.

Problematic perceptions included mention by both groups that the use of insecticide-treated nets, may cause skin irritations and allergies. Both community members and health professionals said malaria is “an impossible disease to eliminate because it is intrinsically associated with forest landscapes.” They concluded that such perceptions can be a barrier to control and elimination.

Efforts to eliminate malaria from low transmission settings are an essential to the overall global goals. These four articles tell us that close attention to and better understanding of humans, parasites and mosquitoes is still needed to achieve these goals.

Below we highlight some of the news we have shared on our Facebook Tropical Health Group page during the past week.

Polio Persists

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?

Malaria Updates

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.

WHO says, “Malaria elimination and universal health coverage go hand in hand,” at a special event during the 72st World Health Assembly. To achieve zero malaria, the goal of involving everyone from the policy maker to the community member must have a focus on achieving universal health coverage (UHC) of all malaria interventions ranging from insecticide treated bednets (ITNs) to appropriate provision of malaria diagnostics and medicines. Many of the studies to date have focused on ITNs, which include long-lasting insecticide treated nets (LLINs), but nationwide monitoring through the Demographic and Health Surveys (DHS), the Malaria Indicator Surveys (MIS) and the Multi-Indicator Cluster Surveys (MICS).

UNICEF’s website provides a data repository that includes the most recent DHS, MIS and MICS survey data per country between 2014 and 2017. For the indicator of one ITN per to people in a household, shows Angola at only 13%, most countries for which recent data are available reached between 40-50%. Only two achieved above 60% on a point-in-time survey, Uganda at 62% and Sao Tome and Principe at 95%. The website shows information that where there were multiple surveys in a country during the period, there were variations, sometimes quite wide, over the years. Aside from the fact that the surveys may have had slightly different procedures, the problem remains of achieving and sustaining UHC for ITNs.

Another factor that affects maintaining UHC for ITNs, assuming the target can be met is the durability of nets. The physical integrity as well as the insecticide efficacy can decline over time. Intact nets may lose their insecticide through improper washing and drying, yet still prevent mosquito bites to the individual sleeping under them. Nets with holes may still maintain a minimal level of effective insecticide and may not fully prevent bites but ultimately kill the mosquito that flies through. Researchers in Senegal have been grappling with these challenges.

Program managers must themselves grapple with whether such compromised nets count toward universal coverage as well as how often to conduct net replacement campaigns. A report from community surveys in Uganda during 2017 found that, “Long-lasting insecticidal net ownership and coverage have reduced markedly in Uganda since the last net distribution campaign in 2013/14.” UHC for ITNs is always a moving target.

A frequently unaddressed issue in seeking to improve ITN coverage is whether it makes a difference in malaria disease. A study in Malawi reported that although ITNs per household increased from 1.1 in 2012 to 1.4 in 2014, the prevalence of malaria in children increased over the period from 28% to 32%. The authors surmised that factors such as insecticide resistance, irregular ITN use and inadequate coordinated use of other malaria control interventions may have influenced the results. This shows that UHC for ITNs cannot be viewed in isolation.

This brings up the issue of the role of the many different vector control measures available. Researchers in Côte d’ Ivoire examined the use of eave nets and window screening. At present eave nets are mainly deployed in research contexts but use of window and door screening and netting are a commercially available interventions that households employ on their own. One wonders then whether UHC should focus on how the household and the people therein are protected by any malaria vector intervention.

Here the discussion should focus on the question raised by colleagues in the USAID/PMI Vectorworks Project. WHO declared a goal of universal ITN coverage in 2009 using the target f one ITN/LLIN for every two household members. Vectorworks found that a decade on only one instance of a country briefly achieving 80% of this UHC net target, whereas no others reached above 60%. In fact, the bigger the household, the less chance there was of meeting the two people for one ITN target. Just because people live in a household that has the requisite number of nets, does not guarantee the actual target for sleeping under a net can be achieved because of practical or cultural realities in a household. Neither the minimal indicator of having at least one net in a household, or the ideal or ‘perfect’ indicator of UHC are satisfactory for judging population protection.

The Vectorworks team suggests that, “Population ITN access indicator is a far better indicator of ‘universal coverage’ because it is based on individual people,” and can be compared to, “The proportion of the population that used an ITN the previous night, which enables detailed analysis of specific behavioral gaps nationally as well as among population subgroups.” Population access to ITNs therefore, provides a batter basis for more realistic policies and strategies.

We have seen that defining as well as achieving universal coverage of malaria interventions is a challenging prospect. For example, do we base our monitoring on households or populations? Do we have the funds and technical capacity to implement and sustain the level of coverage required to have an impact on malaria transmission and move toward elimination? Are we able to introduce new, complimentary and appropriate interventions as a country moves closer to elimination?

A useful perspective would be determination if households and individuals even benefit from any part of the malaria package, even if everyone does not have access and utilize all components. This may be why zero malaria has to start with each person living in endemic areas.