Tropical Health Matters

This year the Annual Meeting of the American Society of Tropical Medicine and Hygiene is virtual. We will feature some of the abstracts over the coming week. Our first selection from the 69th meeting is a study from Rwanda on indoor residual spraying by Michee S. Kabera (see author list and affiliations at end) wherein we learn about the benefits of averting malaria cases.

IRS in Ngoma District

Malaria remains a major public health problem and is among the leading causes of morbidity and mortality in Rwanda. Indoor Residual Spraying (IRS) is a core vector control intervention in Rwanda that supplement Insecticide-treated bed nets (ITNs). Ngoma district is located in Eastern province of Rwanda bordering with Burundi in South. The first IRS round was conducted in the above district in April 2019 (before the high peak season of May-June) with the support of the Government of Rwanda and The Global Funds.

The IRS coverage rate was 98.9% with a protected population of 357,058 using “Pirimiphos methyl 300 CS. Using RHMIS, we compared malaria cases respectively reported for a period of 12 months before IRS (April 2018 to March 2019) and after IRS (April 2019 to March 2020). The total number of uncomplicated malaria cases was significantly dropped down by 82%, from 581,742 before IRS to 105,120 cases after IRS. The incidence per 1000 inhabitants decreased from 1,502 to 265 respectively.

Moreover, the inpatient cases also significantly decreased by 87.7%, from 1037 before IRS to 170 cases after IRS. The cost of conducting IRS in Ngoma district was USD 2,104,007 including both the cost for Insecticides and operation. The invested cost per averted malaria case was USD 4.4. Using the minimum average cost of USD 8.6 for treating an episode of the disease including direct cost and the opportunity costs of travel and waiting time (1,2); the total benefit due to averted malaria cases is estimated to USD 4,132,313.

Applying the average cost for inpatient malaria case which is estimated to USD US$60.44 (4), the benefit due to the averted malaria inpatient cases is equal to USD 52,401. The total benefit for averted outpatients and inpatients is estimated to USD 4,184,714. In conclusion, there was a significant decrease of out and inpatient malaria cases just one year after IRS in Ngoma district.

Furthermore, if we compare the IRS expenditures and the benefits related to the averted malaria cases, there was an important cost benefit. We expect more economic impact as malaria cases may continue to decrease.

Authors and Affiliations

Michee S. Kabera(1), Noella Noella(2), Emmanuel Hakizimana(1), Dunia Munyakanage(1), Jean Louis Mangala(1), Kaendi Munguti(3), Aimable Mbituyumuremyi(1) 1.Rwanda Biomedical Center, Kigali, Rwanda, 2.JHPIEGO, Kigali, Rwanda, 3.President’s Malaria Initiative, Kigali, Rwanda

The American Journal of Tropical Medicine and Hygiene has several new articles on malaria. Abstracts are shared. Two articles examine the role of travel in malaria transmission, both cross-border and rural-urban. Another considers the effect on pharmacokinetics of lumefantrine due to gut bacteria. In Uganda indoor spraying has reduced transmission, but asymptomatic cases remain among children. The challenges of asymptomatic malaria to elimination efforts is also examined in India. Links to the articles are found below.

Evidence of Microbiome–Drug Interaction between the Antimalarial Lumefantrine and Gut Microbiota in Mice

The antimalarial drug lumefantrine exhibits erratic pharmacokinetics. Intersubject variability might be attributed, in part, to differences in gut microbiome–mediated drug metabolism. We assessed lumefantrine disposition in healthy mice stratified by enterotype to explore associations between the gut microbiota and lumefantrine pharmacokinetics. Gut microbiota enterotypes were classified according to abundance and diversity indices from 16S rRNA sequencing. Pharmacokinetic parameters were computed using noncompartmental analysis. Two distinct enterotypes were identified.

Maximal concentration (C max) and total drug exposure measured as the area under the drug concentration–time curve (AUC0–24) differed significantly between the groups. The mean and standard deviation of C max were 660 ± 220 ng/mL versus 390 ± 59 ng/mL (P = 0.02), and AUC0–24 was 9,600 ± 2,800 versus 5,800 ± 810 ng × h/mL (P = 0.01). In healthy mice intragastrically dosed with the antimalarial drug lumefantrine in combination with artemether, lumefantrine exposure was associated with gut bacterial community structure. Studies of xenobiotic–microbiota interactions can inform drug posology and elucidate mechanisms of drug disposition.

Malaria Transmission, Infection, and Disease following Sustained Indoor Residual Spraying of Insecticide in Tororo, Uganda

Tororo, a district in Uganda with historically high malaria transmission intensity, has recently scaled up control interventions, including universal long-lasting insecticidal net distribution in 2013 and 2017, and sustained indoor residual spraying (IRS) of insecticide since December 2014. We describe the burden of malaria in Tororo 5 years following the initiation of IRS. We followed a cohort of 531 participants from 80 randomly selected households in Nagongera subcounty, Tororo district, from October 2017 to October 2019. Mosquitoes were collected every 2 weeks using CDC light traps in all rooms where participants slept, symptomatic malaria was identified by passive surveillance, and microscopic and submicroscopic parasitemia were measured every 4 weeks using active surveillance. Over the 2 years of follow-up, 15,780 female anopheline mosquitos were collected, the majority (98.0%) of which were Anopheles arabiensis.

The daily human biting rate was 2.07, and the annual entomological inoculation rate was 0.43 infective bites/person/year. Only 38 episodes of malaria were diagnosed (incidence 0.04 episodes/person/year), and there were no cases of severe malaria or malarial deaths. The prevalence of microscopic parasitemia was 1.9%, and the combined prevalence of microscopic and submicroscopic parasitemia was 10.4%, each highest in children aged 5–15 years (3.3% and 14.0%, respectively). After 5 years of intensive vector control measures in Tororo, the burden of malaria was reduced to very low transmission levels. However, a significant proportion of the population remained parasitemic, primarily school-aged children with submicroscopic parasitemia, providing a potential reservoir for malaria transmission.

Malaria Diagnosed in an Urban Setting Strongly Associated with Recent Overnight Travel: A Case–Control Study from Kampala, Uganda

Malaria is frequently diagnosed in urban Kampala, despite low transmission intensity. To evaluate the association between recent travel out of Kampala and malaria, we conducted a matched case–control study. Cases were febrile outpatients with a positive malaria test; controls were febrile outpatients with a negative test. For every two cases, five controls were selected, matching on age. Data were collected on recent overnight travel out of Kampala (past 60 days), destination and duration of travel, and behavioral factors, including sleeping under an insecticide-treated net (ITN) during travel. From July to August 2019, 162 cases and 405 controls were enrolled. The locations of residence of cases and controls were similar. More controls were female (62.7% versus 46.3%, P < 0.001). Overall, 158 (27.9%) participants reported recent overnight travel.

Travelers were far more likely to be diagnosed with malaria than those who did not travel (80.4% versus 8.6%, OR 58.9, 95% CI: 23.1–150.1, P < 0.001). Among travelers, traveling to a district not receiving indoor residual spraying of insecticide (OR 35.0, 95% CI: 4.80–254.9, P < 0.001), no ITN use (OR 30.1, 95% CI: 6.37–142.7, P < 0.001), engaging in outdoor activities (OR 22.0, 95% CI: 3.42–141.8, P = 0.001), and age < 16 years (OR 8.36, 95% CI: 2.22–56.2, P = 0.03) were associated with increased odds of malaria. Kampala residents who traveled overnight out of the city were at substantially higher risk of malaria than those who did not travel. For these travelers, personal protection measures, including sleeping under an ITN when traveling, should be advocated.

Prevalence of Asymptomatic Malaria Parasitemia in Odisha, India: A Challenge to Malaria Elimination

The prevalence of malaria in India is decreasing, but it remains a major concern for public health administration. The role of submicroscopic malaria and asymptomatic malaria parasitemia and their persistence is being explored. A cross-sectional survey was conducted in the Kandhamal district of Odisha (India) during May–June 2017. Blood samples were collected from 1897 individuals for screening of asymptomatic parasitemia. Samples were screened using rapid diagnostic tests (RDTs) and examined microscopically for Plasmodium species. Approximately 30% of randomly selected samples (n = 586) were analyzed using real-time PCR (qPCR), and the genetic diversity of Plasmodium falciparum was analyzed.

The prevalence of Plasmodium species among asymptomatic individuals detected using qPCR was 18%, which was significantly higher than that detected by microscopy examination (5.5%) or RDT (7.3%). Of these, 37% had submicroscopic malaria. The species-specific prevalence among asymptomatic malaria-positive cases for P. falciparum, Plasmodium vivax, and mixed infection (P. falciparum and P. vivax) by qPCR was 57%, 29%, and 14%, respectively. The multiplicity of infection was 1.6 and 1.2 for the merozoite surface protein-1 gene (msp1) and (msp2), respectively. Expected heterozygosity was 0.64 and 0.47 for msp1 and msp2, respectively. A significant proportion of the study population, 105/586 (18%), was found to be a reservoir for malaria infection, and identification of this group will help in the development of elimination strategies.

Travel Is a Key Risk Factor for Malaria Transmission in Pre-Elimination Settings in Sub-Saharan Africa: A Review of the Literature and Meta-Analysis

By sustaining transmission or causing malaria outbreaks, imported malaria undermines malaria elimination efforts. Few studies have examined the impact of travel on malaria epidemiology. We conducted a literature review and meta-analysis of studies investigating travel as a risk factor for malaria infection in sub-Saharan Africa using PubMed. We identified 22 studies and calculated a random-effects meta-analysis pooled odds ratio (OR) of 3.77 (95% CI: 2.49–5.70), indicating that travel is a significant risk factor for malaria infection.

Odds ratios were particularly high in urban locations when travel was to rural areas, to more endemic/high transmission areas, and in young children. Although there was substantial heterogeneity in the magnitude of association across the studies, the pooled estimate and directional consistency support travel as an important risk factor for malaria infection.

Recent news and abstracts include mosquito control using solar disruption of of larval habitats and plants that repel the insects around homes. The challenges of malaria related anemia in pregnancy is discussed. Malaria cases increase in Mali and Mozambique, but in the latter, deaths actually decrease. Malaria parasites have ways of making people more attractive to mosquito bites. Finally covid-19 has not disrupted malaria work as much as anticipated. Read more at the links in the sections below.

Improved Mosquito Control with Solar Power Machine that Causes Ripple Effect

Kristina Panos writes that mosquito haters of the world, rejoice! A few years ago we told you about the first version of this solar-powered mosquito repellent that works by disturbing the surface of standing water. Since then, the project has received worldwide attention, and [Pranav] is back with Solar Scare Mosquito version 2.0 in time for the the 2020 Hackaday Prize.

The idea’s still the same as before: let mosquitoes lay their eggs in the standing waters of tanks and swamps, then disturb the water with vibrations so the larvae on the surface can’t breathe. As smart as this simple idea is, version 2.0 is even smarter. It has a microphone that listens to the wing-beat frequencies of mosquitoes that like to hang around places like that. Inside there’s an Arduino MKR GSM to run the ripple-generating air pump, detect water from the sensor, and gather data from the microphone.

With a network of these devices all reporting data, [Pranav] envisions an early warning system for mosquito-borne epidemics that works by alerting the locals through their phones. Solar Scare Mosquito has come a long way since 2014.

Malaria cases spike in northern Mali

Malaria cases in northern Mali have spiked, according to medical workers, claiming 23 lives in the often lawless desert region last week alone. Mali’s ministry of health said this week that 59 people have died of malaria in the north since the start of the year, almost double the number of deaths over the same period last year.

Already struggling to curb coronavirus, the poor Sahel country is also fighting a brutal jihadist insurgency active in the north and centre of the country.

A powerful attractant: Malaria parasites lure blood-sucking mosquitoes

The malaria parasite’s gametocyte-stage has been demonstrated in the field to heavily manipulate the blood-seeking behaviour of vector mosquitoes through increasing the appeal of biting an infected host.

Plasmodium parasites, the causative agents of Malaria in humans and animals, are well known for manipulating both their human and mosquito hosts as a way of maximising the probability of interactions between them, thereby increasing the chance malaria parasites are transmitted from host to host. One way in which these devious parasites have been shown to increase the probability of host interaction is during their transmissible (gametocyte) stage.

This is achieved by inducing host red blood cells to produce volatile compounds that attract malarial vector species, such as mosquitos in the Anopheles family. The increase in production of volatile compounds, such as certain aldehydes and terpenes, by host red blood cells was shown back in 2017 to be specifically induced by a gametocyte-produced molecule called (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate, also known as HMBPP.

Malaria campaigns fight off Covid disruptions to deliver programmes

Almost all planned work against the disease has gone ahead this year, delivering nets, drugs and the world’s first malaria vaccine. More than 90% of anti-malaria campaigns planned this year across four continents are on track, despite disruptions caused by the coronavirus pandemic, according to new research.

The delivery of insecticide-treated nets and provision of antimalarial medicines in the majority of malaria-affected countries across Africa, Asia and the Americas were still going ahead, a high-level meeting organised by the RBM Partnership to End Malaria heard on Thursday.

Malaria associated with increased prevalence of anemia during pregnancy

Ken Downey Jr. and colleagues conducted a study in seven sub-Saharan African countries demonstrated an association between malaria and an increased prevalence of anemia among pregnant women, according to findings published in BMC Pregnancy and Childbirth.

“Pregnant women in sub-Saharan Africa suffer a double burden of malaria and HIV infections, and these infections interact with each other to cause anemia,” Ssentongo told Healio. “If not treated, the risk of the mother and the unborn baby dying is high. Multipronged strategies to prevent and treat malaria in HIV pregnant women are critical to ensure the survival of the mothers and their unborn babies.”Paddy Ssentongo, MD, MPH, a research assistant professor at Penn State University,

Mozambique: Malaria Cases Increase, Malaria Death Toll Declines

From January to August, 442 people in Mozambique are known to have died from malaria, according to Health Minister Armindo Tiago. Speaking at the launch of a National Home Spraying Campaign, Tiago said the malaria death toll, in the first eight months of the year, was significantly lower than that recorded in the same period in 2019, when 562 people died of the disease.

But although fewer people are dying of malaria, the number of malaria cases has actually increased – from 7.86 million cases in January-August 2019 to 8.36 million in the same months this year. The number of cases rose by 6.4 per cent, but the number of deaths fell by 21.4 per cent. Thus there is the drive to persuade families to change their behaviour.

The Plants That Keep Mosquitoes Away

Protect outdoor areas from mosquitoes and bugs to enjoy evenings outside. Including the following plants in a home garden can provide homeowners with some important weapons in the war against mosquitoes.

1. Citronella Plants: You may already be familiar with citronella plants, as they are known for emitting a strong smell that mosquitoes find objectionable. This group of plants contain citronellal, the active ingredient commonly found in mosquito repellents like citronella patio candles or sprays.

2. The Mint Family: Some members of the mint family have the power to repel mosquitoes, or at least take the sting out of their bites. Check Lemon Balm, Peppermint, Basil, Lavender, Sage, and Catnip.

3. Flowers: Believe it or not, ornamental plants can actually do double duty and function as mosquito repellents. Even better, these plants love sun and are drought resistant. Marigolds, and their relative, tarragoncontain pyrethrum, an ingredient found in many insect repellents. Verbena is a lemon-scented, easy-to-grow perennial. Citrosum is also named “the mosquito plant,” and is one of the best plants in the game for repelling mosquitoes.

Abstracts and news look at mosquito control measures including screening eaves and indoor residual spraying from Malaria Journal. Mosquito-associated bacteria, fungi, and even viruses represent untapped tools. Finally one can buy and wear a face mask and help eliminate malaria. Click the links to get more information

Evaluating effectiveness of screening house eaves

… a potential intervention for reducing indoor vector densities and malaria prevalence in Nyabondo, western Kenya. Mosquito-proofing of houses using wire mesh screens is gaining greater recognition as a practical intervention for reducing exposure to malaria transmitting mosquitoes. Screening potentially protects all persons sleeping inside the house against transmission of mosquito-borne diseases indoors. The study assessed the effectiveness of house eaves screening in reducing indoor vector densities and malaria prevalence in Nyabondo, western Kenya. 160 houses were selected for the study, with half of them randomly chosen for eaves screening with fibre-glass coated wire mesh (experimental group) and the other half left without screening (control group).

At all the three parasitological follow-up survey points, house screening significantly reduced the malaria prevalence by 100% (p?<?0.001), 63.6% (p?=?0.026), and 100% (p?<?0.001) in the 1st, 2nd and 3rd follow-up surveys respectively. The study demonstrated that house eave screening has potential to reduce indoor vector densities and malaria prevalence in high transmission areas.

Rapid reduction of malaria transmission following the introduction of indoor residual spraying

… in previously unsprayed districts: an observational analysis of Mopti Region, Mali, in 2017. The National Malaria Control Programme (NMCP) of Mali has had recent success decreasing malaria transmission using 3rd generation indoor residual spraying (IRS) products in areas with pyrethroid resistance, primarily in Ségou and Koulikoro Regions. In 2015, national survey data showed that Mopti Region had the highest under 5-year-old (u5) malaria prevalence at 54%—nearly twice the national average—despite having high access to long-lasting insecticidal nets (LLINs) and seasonal malaria chemoprevention (SMC). Accordingly, in 2016 the NMCP and other stakeholders shifted IRS activities from Ségou to Mopti. A set of retrospective, eco-observational time-series analyses were performed using monthly incidence rates of rapid diagnostic test (RDT)-confirmed malaria cases reported in the District Health Information System 2 (DHIS2) from January 2016 until February 2018.

At HFs in communities of Mopti where IRS was introduced in 2017, peak incidence fell by an average of 42% (CI95 31–63%) between these years, a significantly greater decrease (p?=?0.040) almost double what was seen in the comparator HFCAs. The opposite effect was observed in Ségou Region, where peak incidence at those HFs where IRS was withdrawn after the 2016 campaign increased by an average of 106% (CI95 63–150%) from year to year, also a significant difference-in-differences compared to the comparator no-IRS HFs (p?<?0.0001).

Annual IRS campaigns continue to make dramatic contributions to the seasonal reduction of malaria transmission in communities across central Mali, where IRS campaigns were timed in advance of peak seasonal transmission and utilized a micro-encapsulated product with an active ingredient that was of a different class than the one found on the LLINs used throughout the region and to which local malaria vectors were shown to be susceptible. Strategies to help mitigate the resurgence of malaria cases that can be expected should be prioritized whenever the suspension of IRS activities in a particular region is considered.

COVID-19 Mask Raises Money for Malaria Elimination

Goodbye Malaria was founded by African entrepreneurs who truly believe African creativity is the key to solving Africa’s biggest problems. “From saving lives to saving livelihoods – the birth of the Goodbye Malaria mask.”  Mask initiative helps to raise funds support on-the-ground malaria elimination in Southern Africa. it empowers local crafters to create stylish merchandise using Goodbye Malaria’s iconic shwe shwe fabric. Goodbye Malaria co-founder Kim Lazarus said: “We have never asked the public for donations, instead, offering consumers an opportunity to support malaria elimination efforts through their purchase of our merchandise.” (see photo above)

Prospects and Pitfalls: Next-Generation Tools to Control Mosquito-Transmitted Disease

Annual Review of Microbiology reports that Mosquito-transmitted diseases, including malaria and dengue, are a major threat to human health around the globe, affecting millions each year. A diverse array of next-generation tools has been designed to eliminate mosquito populations or to replace them with mosquitoes that are less capable of transmitting key pathogens. Many of these new approaches have been built on recent advances in CRISPR/Cas9-based genome editing. These initiatives have driven the development of pathogen-resistant lines, new genetics-based sexing methods, and new methods of driving desirable genetic traits into mosquito populations.

Many other emerging tools involve microorganisms, including two strategies involving Wolbachia that are achieving great success in the field. At the same time, other mosquito-associated bacteria, fungi, and even viruses represent untapped sources of new mosquitocidal or antipathogen compounds. Although there are still hurdles to be overcome, the prospect that such approaches will reduce the impact of these diseases is highly encouraging.

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.

The novel 2019 coronavirus, also known as COVID-19 and SARS-COV2, is casting a heavy shadow over the 2020 World Malaria Day. People are trying to remain upbeat declaring the tagline “zero malaria starts with me,” but nothing can hide the fear that the current pandemic will both disrupt the current delivery of essential malaria preventive and treatment services, but will have longer term impacts on malaria funding and our capacity to learn new ways to reach malaria elimination goals. As we can see in the graphic to the right, accessible, lifesaving, community-based services may be especially hard hit.

Another ironic image is the indoor residual spray (IRS) team member with a face mask needed for protection from the insecticides being sprayed. When will such teams be able to go back into homes? When can household members actually pack out their belongings so that spraying can commence? When will such masks not be needed for intensive care COVID-19 case management instead?

WHO is urging “countries to move quickly to save lives from malaria in sub-Saharan Africa” because “New analysis supports the WHO call to minimize disruptions to malaria prevention and treatment services during the COVID-19 pandemic.” This will be difficult in high burden countries like Nigeria that are already on lockdown with over 1,000 coronavirus cases detected already. Modeling by WHO and partners has projected, “Severe disruptions to insecticide-treated net campaigns and in access to antimalarial medicines could lead to a doubling in the number of malaria deaths in sub-Saharan Africa this year compared to 2018.”

The Global Malaria Program offers guidance for tailoring malaria interventions to the present circumstances. Great concern is drawn from previous epidemic situations when observing that, “it is essential that other killer diseases, such as malaria, are not ignored. We know from the recent Ebola outbreak in west Africa that a sudden increased demand on fragile health services can lead to substantial increases in morbidity and mortality from other diseases, including malaria. The COVID-19 pandemic could be devastating on its own – but this devastation will be substantially amplified if the response undermines the provision of life-saving services for other diseases.”

Specifically, GMP recommends that national malaria programs should ensure the following:

• a focal point for malaria is a member of the National COVID-19 Incident Management Team.
• continued engagement with all relevant national COVID-19 stakeholders and partners.
• continued access to and use of recommended insecticide-treated mosquito nets (ITNs)
• continuation of planned targeted indoor residual spraying (IRS)
• early care-seeking for fever and suspected malaria by the general population to prevent a spike in severe malaria
• access to case management services in health facilities and communities with diagnostic confirmation through rapid diagnostic tests [RDTs]
• treatment of confirmed malaria cases with approved protocols
• continued delivery of planned preventive services normally provided to specific target populations (SMC, IPTi, IPTp)
• the safety of all malaria personnel and their clients in the process of carrying out the above interventions

In editorial in the American Journal of Tropical Medicine and Hygiene by Yanow and Good address the damaging longer term impact of the present shutdown. “The impacts of research shutdowns will be felt long after the pandemic. Many scientists study diseases that do not share the same obvious urgency as COVID-19 and yet take a shocking toll on human life. For example, malaria infects more than 200 million people and takes the lives of nearly half a million people, mostly young children, each year.1 During laboratory closures and without clinical studies, there will be no progress toward treating and preventing malaria: no progress toward new drugs, vaccines, or diagnostics.”

The case for continuing malaria services to save hundreds of thousands of lives is not difficult to make. The actual implementation during lockdowns and quarantines is a management challenge. The importance of malaria testing to provide patients with appropriate care for the right disease is crucial. The question is whether in resource strapped endemic countries these decisions and management arrangements can be made in a timely fashion and for the long term whether the next generation of research can proceed with much needed new medicines and technologies.

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.

Dr. Noella Umulisa, the Malaria Team Lead or the USAID Maternal and Child Survival Program in Kigali Rwanda shares with us experiences from Rwanda’s recent observance of World Malaria Day 2017.

The Malaria Day celebration took place in Huye districts in the southern Province. Why the southern province? – because among the 10 high endemic districts, 6 are the southern province. Why Huye district? – because IRS has been launched in Huye district yesterday and in another district Nyanza in Southern province.

The ceremony was attended by USAID and WHO representative, local leaders, MOH staff, partners, population of Simbi sector and the guest of honour was Dr Jeannine Condo the Director General of Rwanda Biomedical Center (which houses malaria activities).

A special recognition was given to community health workers (CHWs) who are playing a key role and are on the front line of fighting Malaria through sensitization of the population, testing and treating the population through community case management (iCMM and HBM) of Malaria, and now when a big number of CHWs will be involved in spraying households in their community.

The World Malaria Day celebration in Rwanda is marked by different activities for Malaria prevention conducted at community level from 24th to 29th April 2017.  Also, Malaria prevention and control messages are being disseminated using different communication tools and approaches such as radio and TV programs, community outreach activities, educating communities on proper use of bed nets.

Door to door mobilization is being conducted about the Indoor Residual Spraying (IRS) in high malaria burden districts of Huye and Nyanza. MCSP, with support from the US President’s Malaria Initiative, has participated actively in this event by supporting Community outreaches though theatre skits in the first 10 high endemic district.

The Director General made the following statement:

In January 2016, the Government of Rwanda and partners developed a Malaria Contingency Plan in response to the increase in malaria cases. The following interventions were implemented to address malaria rise in Rwanda: A Home Based Management of fever for adults at community level was set up countywide to reduce the malaria burden and prevent severe malaria and death. From Nov 2016 up to March 2017, the country distributed more than 6 million nets in 30 districts ensuring universal coverage of the entire population.

The country has increased access to health services for all through Community Based Health Insurance (CBHI). The Government of Rwanda provides free treatment of malaria to the most vulnerable population (Ubudehe 1&2 categories) to ensure that all financial barriers are no more to hinder the health service delivery for the community. Extension of Indoor residual spraying (IRS) in districts with high malaria burden where 5 out of 8 were sprayed (Nyagatare, Kirehe, Bugesera, Gisagara and Gatsibo).

We hope that this commitment will keep Rwanda on track to control and eventually eliminate malaria.

For many years malaria in pregnancy (MIP) was the proverbial neglected step-child of malaria control programs. Partly this was due to structural problems – the challenge of coordination between different units and departments within a ministry of health – malaria programs and reproductive health programs in separate and parallel divisions.

Another reason for neglect may lie in the fact that it is been difficult to achieve the MDG 5 as outlined in the United Nations’ 2014 Millennium Development Goals Report. One still finds that worldwide, almost 300,000 women died in 2013 from causes related to pregnancy and childbirth. Maternal death is mostly preventable and much more needs to be done to provide care to pregnant women.

Maternal death prevention includes providing pregnant women 3 or more doses of sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment in pregnancy (IPTp) and ensuring women have AND sleep under insecticide treated bednets (ITNs) during antenatal care (ANC). Unfortunately recent Demographic and Health Surveys (DHS) and Malaria Information Surveys (MIS) from endemic countries show slow or stagnating progress in reaching Roll Back Malaria goals of 80% coverage of pregnant women with these interventions. Recent DHS/MIS have found that only 15% of recently pregnant women got two doses of IPTp in Nigeria, with only slightly better coverage in Burkina Faso (46%). Now that targets have shifted to three or more doses, the coverage challenge is even greater.

The irony is that these same DHS reports show that a large proportion (>90%) of pregnant women in malaria endemic countries of Africa get registered for ANC. In order to achieve full coverage of IPTp pregnant women should attend ANC at least four times, but the recommended minimum of four ANC visits is difficult to achieve. According to WHO, “The proportion of pregnant women in developing countries who attended at least four antenatal care visit has increased from approximately 37% in 1990 to about 52% in 2012 but, in low-income countries, only 38% of pregnant women attended four times or more antenatal care during 2006-2013.”

In their article, “The quality–coverage gap in antenatal care: toward better measurement of effective coverage,” Stephen Hodgins and Alexis D’Agostino offer an explanation. They point out that it is not the number of ANC contacts alone that matters; it is the content of each visit that is equally important. They explain that a “coverage gap” exists when women who attended ANC four or more times did not receive the elements of basic package of services spelled out in the concept of Focused Antenatal Care (FANC).

Specific findings from Hodgins and D’Agostino’s DHS review showed that, “Blood pressure and tetanus toxoid performed best, with median quality–coverage gaps of 5% and 18%, respectively. The greatest gaps were for iron–folate supplementation (72%) and malaria prevention (86%).” Simply put, the lesson is that attending ANC does not equal receiving lifesaving maternal health services.

Many factors affect the quality of ANC services ranging from the major gaps in availability of trained health workers at the frontline in endemic countries to poor procurement and supply systems for even the cheapest drugs like SP. Even when health workers are in place, their understanding of and attitudes toward using SP for IPTp may be inadequate. These issues are where the gap between attending ANC and receiving needed services emerges. We will not be able to defeat malaria in pregnancy until we invest in strengthening the whole ANC system and pay better attention of women’s health.

Inyama, P.U., Samdi, L., Nsa, H., Iwuchukwu, N. Suleiman, H., Kolyada, L.,  Dengela, D., Lucas, B., Seyoum, A. and Fornadel, C. Are associated with the PMI/AIRS Project in Nigeria. They presented their experiences with IRS at the recently concluded Multilateral Initiative for Malaria 6th Pan African Malaria Conference in Durban South Africa.  They have shared their presentation here.

The President’s Malaria Initiative’s Africa Indoor Residual project (PMI/AIRS), IRS 2 Task Order 4, executed the year 2 spray operation in Nasarawa Eggon and Doma Local Government Areas (LGA) of Nasarawa State, Nigeria. The objectives of the program being the reduction of malaria – associated morbidity and mortality, a total of 62,592 structures were sprayed.  To measure the impact of the IRS program on the malaria vectors  the proportion of parous mosquitoes in  the  vector population  was determined before and after Indoor Residual Spraying.

One thousand, six hundred and twenty one (1,621) female Anopheles gambiae s.l. specimens drawn from a pool of 3,356  Female Anopheline   mosquitoes  captured by Human Landing Catches  from  three LGAs of Nassarawa Eggon and Doma (intervention areas)  and Lafia (Control) of Nasarawa State Nigeria    were dissected using WHO-recommended techniques for parity. The degree of coiling of ovarian tracheoles was observed  pre-IRS intervention in March 2013  and monthly post IRS intervention up to September 2013. Proportion of parous females was compared pre-and between intervention and control villages. Similarly, pre-and post-spray proportion of parous comparison was made within both intervention and control villages.

Overall, a total of 1,621 ovaries of An. gambiae s.l. were dissected before and after IRS intervention.  Of the ovaries dissected at baseline, 71.43% were parous in Nassarawa Eggon, 76.70% in Doma and 77% in the control area. After IRS in May 2013, it was found that the parity had declined dramatically to 17.69% in Nassarawa Eggon, 27.98% in Doma (p <0.05) while in the control area (Lafia) Parity remained as high as 68%. As insecticide residual efficacy continued to decline, slight increase in parity rate was observed in the intervention areas (38% and 31% in N/Eggon and Doma respectively for September) while it remained high (71%) in the control area for the same month.

This study has shown a reduction in the longevity of Anopheles mosquitoes post spraying as compared to pre-spraying in the intervention villages.   The longevity of the vector was also significantly declined post spraying in the intervention villages as compared to unsprayed villages. The observed reduction of the expectation of life of the vector associated with IRS is promising. But further study is needed to fully understand how this will be translated to reduction of malaria transmission in the area.

We wish to thank all technicians who participated in the entomological surveillance activities and dissection of mosquitoes. This work was funded by the President’s Malaria Initiative. www.africairs.net and info@africairs.net