Tropical Health Matters

Today’s stories cover three continents including Surveillance for imported malaria in Sri Lanka, community perceptions in Colombia and Annual Fluctuations in Malaria Transmission Intensity in 5 sub-Saharan countries. In addition there is an overview of microscopy standards and an Integrated Macroeconomic Epidemiological Demographic Model to aid in planning malaria elimination. We also see how COVID-19 is disturbing Seasonal Malaria Chemoprevention activities in Burkina Faso. Read more by following the links in the sections below.

Will More of the Same Achieve Malaria Elimination?

… Results from an Integrated Macroeconomic Epidemiological Demographic Model. Historic levels of funding have reduced the global burden of malaria in recent years. Questions remain, however, as to whether scaling up interventions, in parallel with economic growth, has made malaria elimination more likely today than previously. The consequences of “trying but failing” to eliminate malaria are also uncertain. Reduced malaria exposure decreases the acquisition of semi-immunity during childhood, a necessary phase of the immunological transition that occurs on the pathway to malaria elimination. During this transitional period, the risk of malaria resurgence increases as proportionately more individuals across all age-groups are less able to manage infections by immune response alone. We developed a robust model that integrates the effects of malaria transmission, demography, and macroeconomics in the context of Plasmodium falciparum malaria within a hyperendemic environment.

The authors analyzed the potential for existing interventions, alongside economic development, to achieve malaria elimination. Simulation results indicate that a 2% increase in future economic growth will increase the US$5.1 billion cumulative economic burden of malaria in Ghana to US$7.2 billion, although increasing regional insecticide-treated net coverage rates by 25% will lower malaria reproduction numbers by just 9%, reduce population-wide morbidity by ?0.1%, and reduce prevalence from 54% to 46% by 2034. As scaling up current malaria control tools, combined with economic growth, will be insufficient to interrupt malaria transmission in Ghana, high levels of malaria control should be maintained and investment in research and development should be increased to maintain the gains of the past decade and to minimize the risk of resurgence, as transmission drops. © The American Society of Tropical Medicine and Hygiene [open-access]

Microscopy standards to harmonise methods for malaria clinical research studies

Research Malaria Microscopy Standards (ReMMS) applicable to malaria clinical research studies have been published in Malaria Journal. The paper describes the rationale for proposed standards to prepare, stain and examine blood films for malaria parasites. The standards complement the methods manual(link is external) previously published by the World Health Organization and UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR). The standards aim to promote consistency and comparability of data from microscopy performed for malaria research and hence to strengthen evidence for improvements in malaria prevention, diagnostics and treatment.

Microscopy is important in both malaria diagnosis and research. It is used to differentiate between Plasmodium species and stages and to estimate parasite density in the blood – an important determinant of the severity of disease. It is also used to monitor the effectiveness of drugs based on the rate at which parasites recrudesce or are cleared from the blood.

While rapid diagnostic tests have replaced microscopy in some contexts, microscopy remains an essential tool to support clinical diagnosis and research. The standardisation of methods allows direct comparisons from studies conducted across different points in time and location. This facilitates individual participant data meta-analyses, recognised as the gold standard approach to generate evidence for improvements in interventions and hence patient outcomes.

Estimating Annual Fluctuations in Malaria Transmission Intensity and in the Use of Malaria Control Interventions in Five Sub-Saharan African Countries

RTS,S/AS01E malaria vaccine safety, effectiveness, and impact will be assessed in pre- and post-vaccine introduction studies, comparing the occurrence of malaria cases and adverse events in vaccinated versus unvaccinated children. Because those comparisons may be confounded by potential year-to-year fluctuations in malaria transmission intensity and malaria control intervention usage, the latter should be carefully monitored to adequately adjust the analyses. This observational cross-sectional study is assessing Plasmodium falciparum parasite prevalence (PfPR) and malaria control intervention usage over nine annual surveys performed at peak parasite transmission. Plasmodium falciparum parasite prevalence was measured by microscopy and nucleic acid amplification test (quantitative PCR) in parallel in all participants, and defined as the proportion of infected participants among participants tested. Results of surveys 1 (S1) and 2 (S2), conducted in five sub-Saharan African countries, including some participating in the Malaria Vaccine Implementation Programme (MVIP), are reported herein; 4,208 and 4,199 children were, respectively, included in the analyses.

Plasmodium falciparum parasite prevalence estimated using microscopy varied between study sites in both surveys, with the lowest prevalence in Senegalese sites and the highest in Burkina Faso. In sites located in the MVIP areas (Kintampo and Kombewa), PfPR in children aged 6 months to 4 years ranged from 24.8% to 27.3%, depending on the study site and the survey. Overall, 89.5% and 86.4% of children used a bednet in S1 and S2, of whom 68.7% and 77.9% used impregnated bednets. No major difference was observed between the two surveys in terms of PfPR or use of malaria control interventions. © The American Society of Tropical Medicine and Hygiene [open-access]

Community perception of malaria in a vulnerable municipality in the Colombian Pacific

Malaria primarily affects populations living in poor socioeconomic conditions, with limited access to basic services, deteriorating environmental conditions, and barriers to accessing health services. Control programmes are designed without participation from the communities involved, ignoring local knowledge and sociopolitical and cultural dynamics surrounding their main health problems, which implies imposing decontextualized control measures that reduce coverage and the impact of interventions. The objective of this study was to determine the community perception of malaria in the municipality of Olaya Herrera in the Colombian Pacific.

A 41-question survey on knowledge, attitudes, and practices (KAP) related to malaria, the perception of actions by the Department of Health, and access to the health services network was conducted. In spite of the knowledge about malaria and the efforts of the Department of Health to prevent it, the community actions do not seem to be consistent with this knowledge, as the number of cases of malaria is still high in the area.

Use of a Plasmodium vivax genetic barcode for genomic surveillance and parasite tracking in Sri Lanka

Sri Lanka was certified as a malaria-free nation in 2016; however, imported malaria cases continue to be reported. Evidence-based information on the genetic structure/diversity of the parasite populations is useful to understand the population history, assess the trends in transmission patterns, as well as to predict threatening phenotypes that may be introduced and spread in parasite populations disrupting elimination programmes. This study used a previously developed Plasmodium vivax single nucleotide polymorphism (SNP) barcode to evaluate the population dynamics of P. vivax parasite isolates from Sri Lanka and to assess the ability of the SNP barcode for tracking the parasites to its origin.

A total of 51 P. vivax samples collected during 2005–2011, mainly from three provinces of the country, were genotyped for 40 previously identified P. vivax SNPs using a high-resolution melting (HRM), single-nucleotide barcode method. The proportion of multi-clone infections was significantly higher in isolates collected during an infection outbreak in year 2007. Plasmodium vivax parasite isolates collected during a disease outbreak in year 2007 were more genetically diverse compared to those collected from other years. In-silico analysis using the 40 SNP barcode is a useful tool to track the origin of an isolate of uncertain origin, especially to differentiate indigenous from imported cases. However, an extended barcode with more SNPs may be needed to distinguish highly clonal populations within the country.

Coronavirus rumours and regulations mar Burkina Faso’s malaria fight

By Sam Mednick, Thomson Reuters Foundation: MOAGA, Burkina Faso – Health worker Estelle Sanon would hold the 18-month-old and administer the SMC dose herself, but because of coronavirus she has to keep a distance from her patients. “If I am standing and watching the mother do it, it’s as if I’m not doing my work,” said Sanon, a community health volunteer assisting in a seasonal campaign to protect children in the West African country from the deadly mosquito-borne disease.

Burkina Faso is one of the 10 worst malaria-affected nations in the world, accounting for 3% of the estimated 405,000 malaria deaths globally in 2018, according to the World Health Organization (WHO). More than two-thirds of victims are children under five. Now there are fears malaria cases could rise in Burkina Faso as restrictions due to coronavirus slow down a mass treatment campaign and rumours over the virus causing parents to hide their children, according to health workers and aid officials.

“COVID-19 has the potential to worsen Burkina Faso’s malaria burden,” said Donald Brooks, head of the U.S. aid group Initiative: Eau, who has worked on several public health campaigns in the country.  “If preventative campaigns can’t be thoroughly carried out and if people are too scared to come to health centres … it could certainly increase the number of severe cases and the risk of poor outcomes.”

During peak malaria season, from July to November, community health workers deploy across Burkina Faso to treat children with seasonal malaria chemoprevention (SMC). This is the second year the campaign will cover the whole country with more than 50,000 volunteers going door-to-door, said Gauthier Tougri, coordinator for the country’s anti-malaria programme. Logistics were already challenging. Violence linked to jihadists and local militias has forced more than one million people to flee their homes, shuttered health clinics and made large swathes of land inaccessible. Now the coronavirus has made the task even harder, health workers said.

People in Cape Verde evolved better malaria resistance in 550 years

Yes, we are still evolving. And one of the strongest examples of recent evolution in people has been found on the Cape Verde islands in the Atlantic, where a gene variant conferring a form of malaria resistance has become more common.

Portuguese voyagers settled the uninhabited islands in 1462, bringing slaves from Africa with them. Most of the archipelago’s half a million inhabitants are descended from these peoples. Most people of West African origin have a variant in a gene called DARC that protects.

Deadly malaria and cholera outbreaks grow amongst refugees as COVID pandemic strains health systems.

Apart from the strain on health facilities during the pandemic, in some countries such as Somalia, Kenya and Sierra Leone, we are seeing that a fear of exposure to COVID-19 has prevented parents from taking their children to hospital, delaying diagnosis and treatment of malaria and increasing preventable deaths. COVID restrictions in some countries have also meant pregnant women have missed antimalarial drugs. Untreated malaria in pregnant women can increase the risk of anaemia, premature births, low birth weight and infant death. According to the World Health Organization (WHO), 80% of programs designed to fight HIV, tuberculosis and malaria have been disrupted due to the pandemic and 46% of 68 countries report experiencing disruptions in the treatment and diagnosis of malaria.

Several reports and studies aim to help understand the malaria parasite and the human behavior surrounding its control. Cultural perceptions in Benin influence treatment seeking. Tracking cases in India aid in elimination efforts. The contrasts between in vivo and in vitro studies are examined. The factors associated with anemia among children and women in Ghana are traced to malaria and other factors. Finally both human and mosquito immunity are discussed. Click the links in each section to read details.

Demonstration of indigenous malaria elimination through Track-Test-Treat-Track (T4) strategy in a Malaria Elimination Demonstration Project in Mandla, Madhya Pradesh

Using the current intervention and prevention tools along with optimum utilization of human resources,This project has revealed about 91% reduction of indigenous cases of malaria during the period from June 2017 to May 2020, through case management and vector control strategies. A total 357,143 febrile cases were screened, out of which 0.19% were found positive.

The reduction was similar in the three high prevalence blocks of the district. These results reveal that malaria elimination is achievable in India within a stipulated time frame. The reduction of malaria at the community level was further validated when zero malaria cases were diagnosed during hospital and community-based studies in Mandla. Prompt detection and treatment of imported/migratory cases may have prevented outbreaks in the district. This project has demonstrated that field programmes backed by adequate technical, management, operational, and financial controls with robust monitoring are needed for achieving malaria elimination.needed for achieving malaria elimination.

Risk factors for anaemia among Ghanaian women and children vary by population group and climate zone

Anaemia has serious effects on human health and has multifactorial aetiologies. This study aimed to determine putative risk factors for anaemia in children 6-59 months and 15- to 49-year-old non-pregnant women living in Ghana. Data from a nationally representative cross-sectional survey were analysed for associations between anaemia and various anaemia risk factors. National and stratum-specific multivariable regressions were constructed separately for children and women to calculate the adjusted prevalence ratio (aPR) for anaemia of variables found to be statistically significantly associated with anaemia in bivariate analysis. Nationally, the aPR for anaemia was greater in children with iron deficiency (ID; aPR 2.20; 95% confidence interval [CI]: 1.88, 2.59), malaria parasitaemia (aPR 1.96; 95% CI: 1.65, 2.32), inflammation (aPR 1.26; 95% CI: 1.08, 1.46), vitamin A deficiency (VAD; aPR 1.38; 95% CI: 1.19, 1.60) and stunting (aPR 1.26; 95% CI: 1.09, 1.46).

In women, ID (aPR 4.33; 95% CI: 3.42, 5.49), VAD (aPR 1.61; 95% CI: 1.24, 2.09) and inflammation (aPR 1.59; 95% CI: 1.20, 2.11) were associated with anaemia, whereas overweight and obese women had lower prevalence of anaemia (aPR 0.74; 95% CI: 0.56, 0.97). ID was associated with child anaemia in the Northern and Middle belts, but not in the Southern Belt; conversely, inflammation was associated with anaemia in both children and women in the Southern and Middle belts, but not in the Northern Belt. Anaemia control programmes should be region specific and aim at the prevention of ID, malaria and other drivers of inflammation as they are the main predictors of anaemia in Ghanaian children and women.

From Circulation to Cultivation: Plasmodium In Vivo versus In Vitro

Research on Plasmodium parasites has driven breakthroughs in reducing malaria morbidity and mortality. Standard in vitro culture environments differ dramatically from in vivo conditions in nutrient levels, hematocrit, and rheology and have lower variability in gas levels and temperature.

Nutritional and physical differences lead to pronounced, and often rapid, changes in phenomenon, important for understanding virulence in Plasmodium. Parasite drug sensitivity may be altered due to culture adaptation selection, supraphysiological metabolite concentrations, and in vitro media formulations. Parasites propagated in vitro, versus in vivo, show altered transcriptomic and genomic patterns related to virulence factors, metabolism, gametocytogenesis, and more.

Direct-from-host methodologies avoid the impacts of in vitro culture adaptation but limit the types of assessments that can be performed as many experiments either require equipment not readily available in endemic settings or necessitate long-term manipulation….

Between traditional remedies and pharmaceutical drugs: prevention and treatment of “Palu” in households in Benin, West Africa

In Benin, malaria clinical cases, including the larger popular entity called “Palu” are evoked when people get fever. “Palu” is often self-diagnosed and self-medicated at home. This study aimed to describe the use of herbal medicine, and/or pharmaceutical medicines for prevention and treatment of malaria at home and the factors associated with this usage.

Methods. A cross-sectional survey was conducted in Benin in an urban and in a rural area in 2016. Around 600 households in each place were selected by using a random sampling of houses GPS coordinates of the families. The association between socio demographic characteristics and the use of herbal medicine was tested by using logistic regression models.

Results. In Cotonou (urban), 43.64% of households reported using herbal or pharmaceutical medicine to prevent “Palu”, while they were 53.1% in Lobogo (rural). To treat “Palu” in Cotonou, 5.34% of households reported using herbal medicine exclusively, 33.70% pharmaceutical medicine exclusively and 60.96% reported using both. In Lobogo, 4% reported using herbal medicine exclusively, 6.78% pharmaceutical medicine exclusively and 89.22% reported using both. In Cotonou, the factors “age of respondent”, “participation to a traditional form of savings” and “low socioeconomic level of the household” were associated with the use of herbal medicine.

Conclusions. This study shows the strong use of herbal medicine to prevent “Palu” or even treat it, and in this case it is mostly associated with the use of pharmaceutical medicine. It also highlights the fact that malaria control and care seeking behaviour with herbal medicine remain closely linked to household low-income status but also to cultural behaviour. The interest of this study is mostly educational, with regards to community practices concerning “Palu”, and to the design of adapted behaviour change communication strategies. Finally, there is a need to take into account the traditional habits of populations in malaria control and define a rational and risk-free use of herbal medicine as WHO-recommended.

Malaria parasite fools body with protein to dodge immune system

By SHIGEKO SEGAWA: OSAKA- The parasite responsible for malaria generates a look-alike of a human protein to suppress the workings of the immune system, leaving humans “defenseless” against infection, according to Japanese and British researchers.
A team comprised mainly of researchers from Osaka University and the University of Oxford said they hope the finding will help lead to new therapies for the mosquito-borne tropical disease.

As plasmodium is resistant to the immune system, the body’s self-defense system, humans can become infected repeatedly. Three years ago, the researchers realized that when plasmodium infects human red blood cells, it generates proteins called RIFINs, which send out signals for suppressing immunity. During the latest study, the researchers analyzed the structure of RIFIN in detail and found it closely resembles part of the structure of a specific human protein, which is involved in the mechanism for preventing the immune system from staging an attack on the body by mistake.

That protein combines with a molecule that suppresses the workings of the immune system. The scientists found the RIFIN that closely imitates the human protein in shape also combines with the same molecule and dodges attacks of the immune system. “We hope our findings will help develop vaccines and therapeutic drugs for malaria,” said Hisashi Arase, a professor of immunology with Osaka University, who is part of the research team. The research results were published in Nature, the British scientific journal.

Why Do Insect Vectors Not Get Ill from the Microbes They Transmit?

Some Evidence from Malaria-carrying Mosquitos by Kevin Noonan. The conservation of diverse and molecularly well-defined hemocyte types between distantly related mosquito genera and the apparent absence of megacytes in our Ae. aegypti mosquito dataset raise questions as to how the immune systems of these mosquito species have evolved to limit their capacity to transmit parasites and arboviruses to humans. This knowledge will ultimately underpin immunological strategies aimed at interrupting disease transmission by rendering mosquitoes resistant to such pathogens.

The conservation of diverse and molecularly well-defined hemocyte types between distantly related mosquito genera and the apparent absence of megacytes in our Ae. aegypti mosquito dataset raise questions as to how the immune systems of these mosquito species have evolved to limit their capacity to transmit parasites and arboviruses to humans. This knowledge will ultimately underpin immunological strategies aimed at interrupting disease transmission by rendering mosquitoes resistant to such pathogens.