Tropical Health Matters

The concept and goal of eliminating a disease appears simple on the surface, but complications ensue when the words “as a public health problem” are added.  We know that the distinction exists between eradication and elimination with the former being globally and the latter being nationally or regionally. The sum total action of eliminating a disease from all endemic countries therefore results in total global eradication.

The challenge comes when we try to qualify the concept of elimination. The US CDC defined elimination of disease as, “Reduction to zero of the incidence of a specified disease in a defined geographical area as a result of deliberate efforts; continued intervention measures are required.” Thus, there is no more transmission.  Following from this eradication is defined as, “Permanent reduction to zero of the worldwide incidence of infection caused by a specific agent as a result of deliberate efforts; intervention measures are no longer needed.” Penn Medicine summarized this as, “Elimination means stopping the transmission of a disease in a specific geographic area or country, but not worldwide. Elimination is a crucial step in the path toward eradication, requiring constant monitoring and interventions to keep serious diseases at bay.”

The foregoing definitions seem straightforward, but what does elimination as a public health problem or a disease of public health concern mean? The World Health Organization recently “congratulate(d) Benin and Mali for eliminating trachoma as a public health problem. Concerning another neglected tropical disease (NTD), lymphatic filariasis (LF), global control programs are aiming “to reduce the prevalence of infection below target thresholds and to alleviate the suffering of people affected by lymphoedema and hydrocele.” Wiegand and colleagues in The Lancet Global Health note that, “For schistosomiasis, the criterion for elimination as a public health problem (EPHP) is defined as less than 1% prevalence of heavy-intensity infections (ie, ?50 Schistosoma haematobium eggs per 10 mL of urine or ?400 Schistosoma mansoni eggs per g of stool).” They take issue with the fact that such definitions mean that morbidity still exists, though at very levels, so elimination of transmission has not really occurred for any of these NTDs.

Because the social, environmental, and behavioral conditions that favor transmission may still exists, one cannot guarantee that incidence such diseases may not increase again. All three diseases, LF, Schistosomiasis, and Trachoma have been tackled primarily through preventive chemotherapy, is simply put, using mass drug administration (MDA) over a period of years until active surveillance determines that “infection (is) below target thresholds.” Trachoma does have its SAFE strategy which includes water, sanitation and hygiene interventions, but drugs can reduce the disease without long term achievements in such activities have become sustainable.

Prada et al. in the Journal of Infectious Diseases warn that there can be resurgence of a disease that was documented to be eliminated as a public health problem. They explain that the transmission assessment survey held after several MDA rounds for LF may not be enough to guarantee that low levels of transmission and eventual elimination are achieved. They conclude that, “The risk of resurgence after achieving current targets is low and is hard to predict using just current prevalence. Although resurgence is often quick (<5 years), it can still occur outside of the currently recommended post-intervention surveillance period of 4–6 years,” and recommend monitoring beyond this period.

Toor and co-researchers suggest for NTD programs that, “as case numbers drop and elimination comes into prospect, transmission reduction through other interventions, such as vector control and sanitation, becomes crucial in reducing the probability and speed of resurgence, particularly when MDA or screening programs are halted. Surveillance activities for detecting elimination and resurgence become increasingly important to ensure that successes are maintained.”

Ultimately, unless the context of NTD transmission is addressed, elimination will be an elusive goal. Therefore, as WHO advocated on the recent World NTD Day, “Everybody, including leaders and communities, to confront the inequalities that drive NTDs and to make bold, sustainable investments to free the world’s most vulnerable communities affected by NTDs from a vicious cycle of disease and poverty.”

A May 28^th press release from the World Health Organization states that, “Togo eliminates trachoma as a public health problem.” The article explains that …

“Validation of trachoma elimination as a public health problem in Togo was based on evidence. Several population-based trachoma surveys were conducted starting from 2006 to 2017. The 2017 survey using WHO recommended methodology found that the prevalence of key indicators was below the WHO trachoma elimination threshold. There was also evidence that Togo’s health system is able to identify and treat new cases of late complications of trachoma.”

This raises the question, is Trachoma gone from Togo or does trachoma continue to exist at some low level whereby, as WHO notes, Togo has joined, “12 other countries that have been validated by WHO for having eliminated trachoma as a public health problem.”

This description of disease elimination contrasts sharply with the global concerns when “health authorities in Malawi have declared an outbreak of wild poliovirus type 1 after a case was detected in a young child in the capital Lilongwe. This is the first case of wild poliovirus in Africa in more than five years.” Wild polio virus had been declared eliminated in Africa, and just one case in one country grabs international attention.

Would one case of trachoma tomorrow receive the same concern in Togo? Apparently not according to the WHO definition, “Elimination of trachoma as a public health problem is defined as: (i) a prevalence of trachomatous trichiasis (TT) “unknown to the health system” of < 1 case per 1000 total population; and (ii) a prevalence of trachomatous inflammation-follicular (TF) in children aged 1–9 years of < 5%, in each formerly endemic district.”

So, while no cases of smallpox, guinea worm or polio would be tolerated after elimination has been declared, parents of a child who develops trachoma in Togo tomorrow would be told that your child’s case is only 1 in a 1000 and not of concern to public health. The caveat is though that “the health system (must be) able to identify and manage incident TT cases.” Presumably, if such management capacity does not exist, the disease in question could spread and elimination would be eliminated.

Another Neglected Tropical Disease, Lymphatic Filariasis, faces the same challenge in terms of elimination status. WHO explained in its guidance that, “In 1997, the 50th World Health Assembly resolved to eliminate LF as a public-health problem (resolution WHA50.29). In response, WHO proposed a comprehensive strategy for achieving the elimination goal that included interrupting transmission in endemic communities and implementing interventions to prevent and manage LF-associated disabilities The LF guidance stresses “Effective monitoring, epidemiological assessment and evaluation are necessary to achieve the aim of interrupting LF transmission,” or in a word Surveillance. There is clear concern for “absence of transmission” and worries about “recrudescence.”

While polio has a vaccine and guinea worm relies on providing safe community water, LF and Trachoma elimination depends on mass drug administration (MDA) at planned intervals until such time as transmission is reduced. All require a strong health system to implement, but the challenges of maintaining MDAs until such time as elimination has been validated is somewhat more challenging. In this context the communication is extremely important. Just because WHO validates the elimination of a disease as a public health problem, does not give policy makers license to ignore that disease. Advocacy is continually needed such that even after apparent elimination, neglected diseases will not be forgotten and health systems themselves not neglected.

In the past week, news has featured challenges to malaria elimination around the globe. Starting in Papua New Guinea which accounted for accounted for 86% of all cases in the Western Pacific Region in 2020. While there are 39% fewer cases in the region since 2000, there was an increase of 300,000 cases between 2019 and 2020. It is mainly in the six countries of the Greater Mekong subregion where progress has been steady.

Moving east to the Brazilian Amazon, one finds wildcat gold mining operations are not only destroying Native American ecosystems but are carving huge holes in the earth which are perfect breeding conditions for mosquitoes. This means that malaria cases among the Yanomami indigenous people living in the Brazilian Amazon have increased by more than 12 times since 2014.

Also within South America, one finds that although Paraguay was certified by the World Health Organization (WHO) as free of local transmission of malaria in 2018, experts are warning that travelers entering the country from areas with malaria transmission could easily reintroduce the disease. Hence vigilance is urged.

Crossing next to sub-Saharan Africa, one reads of studies showing an increasing link between malaria and agriculture across the region. As population expands in the region, more food, water and agricultural commodities are required. Irrigation and deforestation to clear land for agriculture increase the risk of childhood malaria in sub-Saharan Africa. The experts recommend that African ministries of agriculture, health, and environment need to collaborate on safer development policies and practices, not only to curb malaria, but the devastating effects of climate change.

Finally continuing back to Asia, one finds what might be termed an epidemiological conflict between Nepal, which is nearing malaria elimination for 2025, and its southern neighbor India, which is a source of imported malaria. Although the number of indigenous cases is nearing zero, health authorities fear that imported cases of of malaria from India are so high that local transmission could be reignited.

Malaria is clearly a global health problem. Collaboration and coordination across continents is needed to eliminate the scourge.

A just-published article by Andrea Chaves and colleagues entitled, “Presence and potential distribution of malaria-infected New World primates of Costa Rica”, Specifically their results state that, “PCR analysis for the Plasmodium presence was conducted in 384 samples of four primates …

• Howler monkey [n?=?130]
• White-face monkey [n?=?132]
• Squirrel monkey [n?=?50]
• red spider monkey [n?=?72]),

… from across Costa Rica. Three Plasmodium species were detected in all primate species (P. falciparum, P. malariae/P. brasilianum, and P. vivax). Overall, the infection prevalence was 8.9%, but each Plasmodium species ranged 2.1–3.4%. The niche model approach showed that the Pacific and the Atlantic coastal regions of Costa Rica presented suitable climatic conditions for parasite infections. However, the central pacific coast has a more trustable prediction for malaria in primates.”

Last year, Tobias Mourier et al. reported another human/non-human primate connection in Brazil. According to them, “Analysis of the P. simium genome confirmed a close phylogenetic relationship between P. simium and P. vivax, and suggests a very recent American origin for P. simium. The presence of the DBP1 deletion in all human-derived isolates tested suggests that this deletion, in combination with other genetic changes in P. simium, may facilitate the invasion of human red blood cells and may explain, at least in part, the basis of the recent zoonotic infections.

The connection between human and primate malaria also flows toward humans as traditional human plasmodium infections decrease in prevalence in Malaysia. Lai are co-researchers explain that, “The incidence of zoonotic malaria Plasmodium knowlesi infection is increasing and now has been the major cause of malaria in Malaysia.”

In fact, the 2021 World Malaria Report noted that, “Malaysia had no cases of human malaria for 3 consecutive years, but in 2020 reported 2607 cases of P. knowlesi, a zoonotic malaria.” The report does not specify efforts to handle this issue.

These studies raise a continuing question about the feasibility of eliminating malaria in countries when those plasmodium species that infect humans also infect other primates and vice versa. As we have noted before, monkeys do not use bednets. As long as primate Plasmodium reservoirs exist, our ability to eliminate the disease will remain elusive.

Over the coming three days the Malaria Vaccine Implementation Programme (MVIP) Advisory Group in its capacity as SAGE/MPAG Working Group will conduct a full evidence review of the RTS,S/AS01 malaria vaccine and develop proposed recommendations for Strategic Advisory Group of Experts (SAGE) on Immunization and MPAG. This comes on the heels of the recent 74th World Health Assembly Resolution that, “Urges Member States to step up the pace of progress through plans and approaches that are consistent with WHO’s updated global malaria strategy and the WHO Guidelines for malaria. It calls on countries to extend investment in and support for health services, ensuring no one is left behind; sustain and scale up sufficient funding for the global malaria response; and boost investment in the research and development of new tools.”

The large scale pilot intervention of the RTS,S/AS01 malaria vaccine started two years ago in selected districts in three countries countries: Ghana, Kenya and Malawi.  For example, “Two years on from the launch of a pilot programme, more than 1.7 million doses of the world’s first malaria vaccine have been administered in Ghana, benefitting more than 650,000 children with additional malaria protection.” WHO says that, “Insights generated by the pilot implementation will inform a WHO recommendation on broader use of the vaccine across sub-Saharan Africa,” which will then be considered by global advisory bodies for immunization and malaria, i.e. the SAGE and MPAG.

WHO is asking the Working Group to address the following question, “Does the additional evidence on the feasibility, safety and impact of the RTS,S/AS01 vaccine support a WHO recommendation for use of the vaccine in children in sub-Saharan Africa beyond the current pilot implementation?” WHO has set the following meeting objectives:

1. To examine and provide input to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence profiles of the quality of the evidence used to inform the recommendations;
2. To review and interpret the evidence, with explicit consideration of the overall balance of benefits and harms;
3. To formulate recommendations – in alignment with the endorsed 2019 RTS,S Framework for Decision – taking into account benefits, harms, values and preferences, feasibility, equity, acceptability, resource requirements and other factors, as appropriate.

Hopefully decisions will be forthcoming soon so that planning can get underway to address immunization as part of the overall malaria elimination effort.

In 2001 the first Africa Malaria Day (AMD) was observed. The opportunity to mark progress and exhort increased efforts for the continent continued through 2007. Then in 2008, the concept of World Malaria Day (WMD) took over, though it could not be denied that the bulk of malaria morbidity, mortality and intervention still was focused on African countries. Other countries have made progress such as the recent certification of malaria elimination in Argentina and El Salvador, but twenty years after the first AMD/WMD, Africa is still leading the way for creative, sustained intervention against the disease, despite threats to resources from economic downturns and new pandemic diseases.

Below we go straight to Africa to share activities and observances of WMD 2021 from Jhpiego’s African Malaria Technical Officers. After reading through, please watch “Jhpiego Leaves No One Behind | World Malaria Day, 2021″ on YouTube.

“Saramed” from Guinea reports that Guinea, like other countries in the world, celebrates World Malaria Day under the theme: ” Zero Malaria, Draw a Line on Malaria “. We are currently conducting the following activities:

• Lectures and debates on malaria in medical faculties and health schools;
• Animation of debate programs on malaria in public and private radios and televisions of the country,
• Advocacy and sensitization of religious and other influential people
• Carrying out a package of activities (administration of IPT to pregnant women who have missed their ANC appointment, community distribution of LLINs, screening and treatment of confirmed cases, awareness raising on malaria) in high incidence localities.

These activities is in line with the WHO approach of “high burden, high impact”.

Noella Umulisa reports that the WMD celebration took place in Eastern Province, in Bugesera district in the Mareba sector. Due to COVID-19 pandemic ,only 100 persons were invited to the event.This year’s the national theme is “Zero Malaria starts with me”.

Key activities during the event included …

• Visit of breeding sites under sentinel surveillance
• Visit of indoor residual spraying (IRS) sites
• Launching of the Awareness of the population using drones on the ongoing IRS campaign in this time of COVID-19
• Song by CHWs
• Certificate to Integrated Vector Management (IVM) Training of Trainers who will train others up to village level
• Speech of the Director General ,the guest of honor.

From Burkina Faso, Yousseff Sawadogo and Moumouni Bonkoungou shared photos of the celebration that featured a giant Insecticide-Treated  Net, a speech by the US Ambassador, a malaria song composed by a nurse, an official speech by the President of the National Assembly, and national recognition given to one of the current Jhpiego staff members, Thiery Ouedraogo, who at one time also served as director of the national malaria control program. He was decorated by the country’s authorities as a knight of the order of merit.

Bright Orgi from Jhpiego’s TiPToP malaria in pregnancy project in Nigeria ?? shared photos from a series of compound meetings in the community to mark WMD 2021. The meetings focused on malaria prevention and treatment. Provided opportunities to rural communities to ask questions on malaria issues. Here we can see that observance of WMD must be taken to the people who actually suffer from malaria and need to be actively involved in its solution. Deo Cibinda from the Democratic Republic of the Congo share photos of a national celebration, seen to the left.

Finally, As Kristen Vibbert noted, “These are such amazing World Malaria Day stories. I’m so heartened to see all of these great country efforts to remind everyone of how the fight against malaria must continue despite the Covid-19 pandemic.”  Charles Wanga tweeted, “We know how to defeat #malaria. But that’s not enough. We must do more to save pregnant women and children from the deadly scourge. This #WorldMalariaDay and everyday, because@Jhpiego leaves no one behind in our fight to #EndMalaria for good in Africa, and everywhere”

Recent news and abstracts explore malaria on three continents. Genetic aspects of malaria are studied in Haiti as well in Malaysia. Use of fish to control malaria carrying mosquitoes are successful in India. The movement toward malaria elimination is examined in Cape Verde. Finally, Non-invasive diagnostic tests are recognized/rewarded by NIH. Read more by following the links below.

NIH Awards Prize to Hemex Health’s Non-Invasive Sickle Cell, Malaria, Anemia Rapid Test (“SMART”) Diagnostic Technology

Researchers from Hemex Health, Medtronic plc, Case Western Reserve University, and the University of Nebraska Medical Center’s International Foundation Against Infectious Disease in Nigeria (IFAIN) were awarded 3rd place and $100,000 in the NIH Technology Accelerator Challenge.  Code named, SMART (Sickle, Malaria, Anemia, Rapid Test), the system includes non-invasive diagnostics for sickle cell, malaria, and anemia. The project seeks to build on Hemex Health’s Gazelle® platform, which currently includes minimally invasive tests (using a drop of blood) for malaria, the detection and quantification of hemoglobin variants, as well as for total hemoglobin for anemia determination.

The non-invasive test will screen for anemia, malaria, and sickle cell disease using an optical finger sensor similar to the way blood oxygen is measured. An advantage of combining the non-invasive and minimally invasive diagnostics is, when needed, more diagnostic information and confirmation is available on the same platform. The goal is a one-minute, $0.25 non-invasive malaria, sickle cell, and anemia test. “The world desperately needs easy-to-use diagnostic technologies with the flexibility needed to meet viruses and diseases in every corner of the planet,” said Ms. White.

Controlling Mosquitoes: Ramanathapuram district inches closer to malaria-free status

Steps taken by the Ramanathapuram district administration to control mosquito breeding for the last five years has enableed the district inch closer to being declared a ‘malaria-free district, with only one malarial fever case having been reported till September, this year. Last year, the district reported 43 cases.

One of the initiatives is to bring guppy fish from the Ayyankulam tank in Tiruvannamalai district and let them into all wells and tanks of the districts in 3:1 ratio (3 familes/one male). The fish thrives, eating the mosquito larvae and eggs and the incidence of malaria came down in the district.

Updates on malaria epidemiology and profile in Cabo Verde from 2010 to 2019: the goal of elimination

Located in West Africa, Cabo Verde is an archipelago consisting of nine inhabited islands. Malaria has been endemic since the settlement of the islands during the sixteenth century and is poised to achieve malaria elimination in January 2021. The aim of this research is to characterize the trends in malaria cases from 2010 to 2019 in Cabo Verde as the country transitions from endemic transmission to elimination and prevention of reintroduction phases. All confirmed malaria cases reported to the Ministry of Health between 2010 and 2019 were extracted from the passive malaria surveillance system.

A total of 814 incident malaria cases were reported in the country between 2010 and 2019, the majority of which were Plasmodium falciparum. Cabo Verde has made substantial gains in reducing malaria burden in the country over the past decade and are poised to achieve elimination in 2021. However, the high mobility between the islands and continental Africa, where malaria is still highly endemic, means there is a constant risk of malaria reintroduction. Characterization of imported cases provides useful insight for programme and enables better evidence-based decision-making to ensure malaria elimination can be sustained.

Genetic analysis reveals unique characteristics of Plasmodium falciparum parasite populations in Haiti

With increasing interest in eliminating malaria from the Caribbean region, Haiti is one of the two countries on the island of Hispaniola with continued malaria transmission. While the Haitian population remains at risk for malaria, there are a limited number of cases annually, making conventional epidemiological measures such as case incidence and prevalence of potentially limited value for fine-scale resolution of transmission patterns and trends. In this context, genetic signatures may be useful for the identification and characterization of the Plasmodium falciparum parasite population in order to identify foci of transmission, detect outbreaks, and track parasite movement to potentially inform malaria control and elimination strategies.

This study evaluated the genetic signals based on analysis of 21 single-nucleotide polymorphisms (SNPs) from 462 monogenomic (single-genome) P. falciparum DNA samples extracted from dried blood spots collected from malaria-positive patients reporting to health facilities in three southwestern Haitian departments (Nippes, Grand’Anse, and Sud) in 2016.

437 of the 462 samples shared high levels of genetic similarity–at least 20 of 21 SNPS–with at least one other sample in the dataset. These results revealed patterns of relatedness suggestive of the repeated recombination of a limited number of founding parasite types without significant outcrossing. These genetic signals offer clues to the underlying relatedness of parasite populations and may be useful for the identification of the foci of transmission and tracking of parasite movement in Haiti for malaria elimination.

Epidemiology of malaria among pregnant women during their first antenatal clinic visit in the middle belt of Ghana

A total of 1655 pregnant Ghanaian women aged 18 years and above with a gestational age of 13–22 weeks, who attended an antenatal care (ANC) clinic for the first time, were consented and enrolled into the study. A structured questionnaire was used to collect socio-demographic and obstetric data and information on use of malaria preventive measures. Venous blood (2 mL) was collected before sulfadoxine-pyrimethamine administration. Malaria parasitaemia and haemoglobin concentration were determined using microscopy and an automated haematology analyser, respectively.

One out of five pregnant women attending their first ANC clinic visit in an area of perennial malaria transmission in the middle belt of Ghana had Plasmodium falciparum infection. Age???25 years, multigravid, educated to high school level or above, and in household with higher socio-economic status were associated with a lower risk of malaria parasitaemia. Majority of the infections were below 1000 parasites/µL and with associated anaemia. There is a need to strengthen existing malaria prevention strategies to prevent unfavourable maternal and fetal birth outcomes in this population.

Genetic diversity of circumsporozoite protein in Plasmodium knowlesi isolates from Malaysian Borneo and Peninsular Malaysia

Understanding the genetic diversity of candidate genes for malaria vaccines such as circumsporozoite protein (csp) may enhance the development of vaccines for treating Plasmodium knowlesi. Hence, the aim of this study is to investigate the genetic diversity of non-repeat regions of csp in P. knowlesi from Malaysian Borneo and Peninsular Malaysia.
The phylogenetic analysis revealed indistinguishable clusters of P. knowlesi isolates across different geographic regions, including Malaysian Borneo and Peninsular Malaysia.

The csp non-repeat regions are relatively conserved and there is no distinct cluster of P. knowlesi isolates from Malaysian Borneo and Peninsular Malaysia. Distinctive variation data obtained in the C-terminal non-repeat region of csp could be beneficial for the design and development of vaccines to treat P. knowlesi.

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.

News and abstracts provide more on the surge of malaria in Mali. COVID-19 complicates malaria elimination in Southeast Asia. Peace Corps health care for volunteers in Comoros is questioned. Malaria risk in Ecuador is investigated. Risk maps are used/not used in three Sub-Saharan countries. The potential of microbiological control is considered. More information on each topic is available in the links provided.

Health workers raise alarm over surge in malaria cases, deaths in Mali

More details emerge on malaria in northern Mali. Medical workers in Mali raised an alarm over a surge in malaria cases which has seen at least 23 people killed by the disease in just the past one week. About 13,000 malaria cases were reported in the north by medical workers between September 21 and 27, representing an 88 percent increase in cases from the previous week. 59 people have died of malaria in the nation’s northern region since the beginning of the year, according to the ministry, which confirmed the deaths of the 23 people over the aforementioned September period.

Will COVID-19 hamper ASEAN’s fight to eliminate malaria?

Although progress elsewhere in the world has been slow, in the Asia-Pacific, deaths due to the mosquito-borne disease have dropped by 70% and cases have dropped by 22%. Within ASEAN, those figures—according to the Asia Pacific Leaders Malaria Alliance (APLMA)—are 92% and 67% respectively. The battle to eliminate malaria is continually evolving with different species of disease-carrying mosquitoes and parasites presenting new challenges. In 2008, a new strain of malaria that proved resistant to the anti-malarial drug artemisinin, nicknamed “super malaria”, emerged in Cambodia. It spread through the Greater Mekong region into Laos, Thailand and Vietnam and by 2017, it had developed resistance to another drug, piperaquine.

In response, scientists and researchers focused their resources on areas where the new strain was present and were making headway towards eliminating it. COVID-19 could threaten that progress. “We have enough evidence from the Ebola epidemic to suggest how progress on malaria elimination could be derailed and we are seeing some clear warnings now,” APLMA/APMEN commented. Historically, malaria cases have risen in countries where healthcare is interrupted due to conflict, disaster and war.

Peace Corps faces questions over death of volunteer from Inverness

By Sheryl Gay Stolberg of the New York Times reported that the Peace Corps, which suspended all operations for the first time in its history as the novel coronavirus raced around the globe, is facing renewed questions about the quality of its medical care — in particular, after the death of a 24-year-old volunteer from undiagnosed malaria — as it prepares to send volunteers back into the field.

An investigation by the Peace Corps inspector general documented a string of problems with Heiderman’s care. Her doctor had “limited training in tropical medicine,” the investigation found, and failed to test for malaria, which would have revealed that Heiderman had been infected by the deadliest malaria parasite. The Peace Corps was also using outdated 2006 guidelines for malaria, which did not reflect the current standard of care.

Anopheline and human drivers of malaria risk in northern coastal Ecuador

Understanding local anopheline vector species and their bionomic traits, as well as related human factors, can help combat gaps in protection. In San José de Chamanga, Esmeraldas, at the Ecuadorian Pacific coast, anopheline mosquitoes were sampled by both human landing collections (HLCs) and indoor-resting aspirations (IAs) and identified using both morphological and molecular methods.

Among 222 anopheline specimens captured, based on molecular analysis. The exophagic feeding of anopheline vectors in San Jose de Chamanga, when analysed in conjunction with human behaviour, indicates a clear gap in protection even with high LLIN coverage. The lack of indoor-resting anophelines suggests that indoor residual spraying (IRS) may have limited effect. The presence of asymptomatic infections implies the presence of a human reservoir that may maintain transmission.

How useful are malaria risk maps at the country level?

This study examined the perceptions of decision-makers in Kenya, Malawi and the Democratic Republic of Congo. Declining malaria prevalence and pressure on external funding have increased the need for efficiency in malaria control in sub-Saharan Africa (SSA). Modelled Plasmodium falciparum parasite rate (PfPR) maps are increasingly becoming available and provide information on the epidemiological situation of countries. However, how these maps are understood or used for national malaria planning is rarely explored. In this study, the practices and perceptions of national decision-makers on the utility of malaria risk maps, showing prevalence of parasitaemia or incidence of illness, was investigated.

Three different types of maps were used to show malaria epidemiological strata: malaria prevalence using a PfPR modelled map (Kenya); malaria incidence using routine health system data (Malawi); and malaria prevalence using data from the most recent Demographic and Health Survey (DRC). In Kenya the map was used to target preventative interventions, including long-lasting insecticide-treated nets (LLINs) and intermittent preventive treatment in pregnancy (IPTp), whilst in Malawi and DRC the maps were used to target in-door residual spraying (IRS) and LLINs distributions in schools. Maps were also used for operational planning, supply quantification, financial justification and advocacy. Findings from the interviews suggested that decision-makers lacked trust in the modelled PfPR maps when based on only a few empirical data points (Malawi and DRC). Despite the availability of national level modelled PfPR maps in all three countries, they were only used in one country.

Infection of highly insecticide-resistant malaria vector Anopheles coluzzii with entomopathogenic bacteria

This study found that Chromobacterium violaceum reduces its survival, blood feeding propensity and fecundity of mosquitoes in Burkina Faso. The study was motivated by the concern that malaria eradication will not be achieved without the introduction of novel control tools. Microbiological control might be able to make a greater contribution to vector control in the future. The interactions between bacteria and mosquito make mosquito microbiota really promising from a disease control perspective.
Methods

To assess entomopathogenic effects of C. violaceum infection on mosquitoes, three different types of bioassays were performed in laboratory. These bioassays aimed to evaluate the impact of C. violaceum infection on mosquito survival, blood feeding and fecundity, respectively. During bioassays mosquitoes were infected through the well-established system of cotton ball soaked with 6% glucose containing C. violaceum.

The data showed important properties of Burkina Faso C. violaceum strains, which are highly virulent against insecticide-resistant An. coluzzii, and reduce both mosquito blood feeding and fecundity propensities. However, additional studies as the sequencing of C. violaceum genome and the potential toxins secreted will provide useful information render it a potential candidate for the biological control strategies of malaria and other disease vectors.

News focuses on getting a handle on urban malaria in Uganda and Tanzania. Listen to a program on the disease burden of malaria in Africa.  Chad reports a high test positivity rate. Algeria is re-experiencing malaria after it was officially eliminated. Links for more details are found in each section.

Modelling and mapping the intra-urban spatial distribution of Plasmodium falciparum parasite rate using very-high-resolution satellite derived indicators

Stefanos Georganos, Oscar Brousse, Moritz Lennert, and others in International Journal of Health Geographics report on the rapid and often uncontrolled rural–urban migration in Sub-Saharan Africa is transforming urban landscapes expected to provide shelter for more than 50% of Africa’s population by 2030. Case studies include two Sub-Saharan African cities, Kampala and Dar es Salaam.

Openly accessible land-cover, land-use, population and OpenStreetMap data were employed to spatially model Plasmodium falciparum parasite rate standardized to the age group 2–10 years (PfPR2–10) in the two cities through the use of a Random Forest (RF) regressor. The RF models integrated physical and socio-economic information to predict PfPR2–10 across the urban landscape. Intra-urban population distribution maps were used to adjust the estimates according to the underlying population.

The results suggest that the spatial distribution of PfPR2–10 in both cities is diverse and highly variable across the urban fabric. Dense informal settlements exhibit a positive relationship with PfPR2–10 and hotspots of malaria prevalence were found near suitable vector breeding sites such as wetlands, marshes and riparian vegetation. In both cities, there is a clear separation of higher risk in informal settlements and lower risk in the more affluent neighborhoods. Additionally, areas associated with urban agriculture exhibit higher malaria prevalence values. This study demonstrates the importance of remote sensing as an epidemiological tool for mapping urban malaria variations at large spatial extents, and for promoting evidence-based policy making and control efforts.

Malaria: Africa’s nagging health burden

Listen to Episode Nine of Africa Science Focus is on malaria, which is one of the biggest killers on the continent. “Malaria is so common you can get it anywhere, anyhow, any time,” Jessica, a malaria sufferer in Liberia, tells the programme. This is because Africa’s mosquitoes are “supremely efficient vectors of malaria disease”, says the World Health Organization’s David Schellenberg.

Malaria: More than 500K cases reported in Chad, Deadliest disease in country

According to data from the National Committee for Epidemic Control (CTNLE), out of the 943,040 malaria tests conducted between 1 January and 13 September 2020, a total of 571,258 cases were confirmed (60.5 percent), with 1,280 deaths across the country. In addition close to 1,140,000 suspected cases based on clinical symptoms but who have not been tested. Among these suspected cases, 1,368 people have died. The most affected provinces are, among others, Logone oriental (with a total of 80,930 cases), Mandoul (82 258 cases), Moyen-Chari (60 207 cases), Tandjle (55 777 cases) and N’Djamena (53 976 cases).

Officials say the situation is slightly better than last year around the same period when 689,563 cases were confirmed and 1,323 died – a difference of 118,305 cases and 43 deaths. However, the situation has worsened compared to 2017 and 2018 when the number of confirmed cases were 524,148 and 534,781 (with 957 and 922 deaths) respectively.

Algeria faces new malaria cases one year after victory over deadly disease

Algeria Tuesday registered over 1,000 cases of malaria, one year after the World Health Organization (WHO) declared the country malaria-free. The cases, according to the health ministry, are imported cases and have been spotted in five governorates namely Tamanrasset (918), Adrar (96), Illizi (89), Ouargla (5) and Ghardaïa (2).

The ministry noted that every year, in September after first rains, the country often registers imported malaria cases, hailing from Sahel neighboring countries or Algerians who sojourned in those countries. The WHO in May 2019, declared Algeria malaria-free. The certification is awarded to countries after three straight years of zero home-born cases of malaria.