Posts or Comments 19 March 2024

Archive for "Diagnosis"



Children &COVID-19 &Diagnosis &IPTp &ITNs &Malaria in Pregnancy &Treatment Bill Brieger | 06 Oct 2022

2021 DHS and MIS Findings from Six Malaria Endemic Countries

The Demographic and Health Survey Program has released final and summary reports for both DHS and Malaria Indicator Surveys (MIS) for 2021 from several malaria endemic African countries. Below is a brief summary of some of the findings from Madagascar, Nigeria, Burkina Faso, Mali, Côte d’Ivoire, and Senegal. Click the link on each country to download a copy for yourself.

The proportion of the population who slept under an insecticide treated bednet the night before the survey varied. In Madagascar it was 49%, While in Nigeria it was 59%. Mali achieved the highest coverage at 73%, while Burkina Faso had the lowest previous night coverage at 41%.

Senegal showed a worrying decrease from 63% in 2016 to 46% in 2021. Côte d’Ivoire did not report total household use, but indicated that 72% of homes had at least one net, with 58% of children below 5 years of age and 64% of pregnant women sleeping under them.

At least three doses of sulfadoxine-pyremethamine is recommended for Intermittent preventive treatment of malaria in pregnant women. The national average was 38% for at least 3 doses in Senegal, although ironically 92% had been reached with the first dose. In Mali only 35% received at least a third dose. Burkina Faso started out with 92% for the first dose, but reached 57% with three or more. Côte d’Ivoire started with 80% receiving their first dose and concluded with only 35% receiving a third. Both Madagascar and Nigeria had the lowest 3-dose coverage at 31%.

Malaria testing and treatment using rapid diagnostic tests and artemisinin-based combination therapy (ACT) was reported. Nigeria demonstrates the challenges of following guidelines. Although 63% of children under 5 years of age were reported to have had a fever in the two weeks preceding the survey, only 24% of those received a diagnostic test. The summary results report that 74% of those with fever “who took any anti-malaria medicine” used the recommended ACT. The implication is that many received medicine without confirmatory testing such that some may have gotten ACT who needed another medicine and some who actually had malaria may have missed the correct treatment.

A similar low level of testing was seen in Senegal (22%), Mali (23%), and Madagascar (20%). Côte d’Ivoire reported 38% of febrile children having been tested. Burkina Faso performed better for testing with 65%.

These brief findings indicate that implementation of Malaria interventions are far from ideal. We know that some of the blame can be placed on health service disruptions due to demands of COVID-19 activities by health ministries and partners. Still, with 8 years remaining until 2030, Reinvigorated efforts are needed in all endemic countries if these six examples are indicative of the challenges we face.

Community &Diagnosis &Guidelines &Health Workers &IPTp &Malaria in Pregnancy &Monitoring &Treatment Bill Brieger | 02 Nov 2021

Updating Malaria Guidelines and Tools: The Kenya Example

Kenya Division of National Malaria Program (DNMP) with support from PMI Impact Malaria (IM) and in collaboration with other stakeholders reviewed/developed/updated nine key program documents. Agustine Ngindu and the Impact Malaria/PMI team stress the importance of keeping key malaria technical guidance and tools up-to-date.

Guidelines for the Diagnosis, Treatment, and Prevention of Malaria in Kenya was revised to indicate the start of IPTp at 13 weeks from the prior recommendation of 16 weeks of gestation and updated the IPTp schedule in line with WHO guidance. The program also updated dosing charts for artemether lumefantrine, dihydroartemisinin-piperaquine, and injectable artesunate to include both weight and age range particulars. This update will enhance adherence to treatment guidelines among healthcare workers

The Kenya Quality Assurance Guidelines for Parasitological Diagnosis of Malaria was in draft form for nearly 10 years. Revisions were motivated by the lack of a functional quality assurance (QA)/quality control (QC) system for malaria diagnosis. Sections were added to guide implementation of internal quality control and external quality assurance programs. Updates also provided guidance on surveys to determine the extent of gene deletion and its effect on routine RDT-based malaria diagnosis.

Implementation Framework for Malaria Rapid Diagnostic Tests was developed to facilitate rollout of malaria diagnostics QA/QC in line with Kenya Malaria Strategy (KMS) of 2019-2023. As p[art of this effort, the M&E framework was expanded to include the performance matrix. A costed implementation matrix to provide guidance was developed on costing of activities in line with KMS 2019-2023.

Biosafety Guidelines for Malaria Rapid Diagnostic Testing at Community Level was highlighted in new guidelines developed to address emerging QA and biosafety concerns at community level. This was a response to requirements by the Kenya Medical Laboratory Technicians and Technologists Board to allow for a new waiver for community health volunteers (CHVs) to conduct testing using mRDTs.

The Guidelines on Community Case Management of malaria and its implementation plan were strengthened as was the Implementation framework for Rapid Diagnostic Testing. Updated job aids included dosing schedules for artemether lumefantrine (AL) and injectable artesunate for use at service delivery points by Health Care Workers in line with the revised guidelines.

Hopefully all national malaria programs will take the Kenya experience as an example of the need to update regularly all the tools needed for front line staff to achieve malaria elimination.

Anemia &Diagnosis &Elimination &Epidemiology &Genetics &Integrated Vector Management &IPTp &Malaria in Pregnancy &Plasmodium knowlesi Bill Brieger | 26 Oct 2020

Malaria News Today 2020-10-26: Haiti, India, Malaysia, Cape Verde

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.

Agriculture &Diagnosis &Elimination &Mapping &Urban Bill Brieger | 01 Oct 2020

Malaria News Today 2020-10-01

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.

Costs &Diagnosis &Ecosystems &Elimination &Genetics &IPTp &ITNs &Microscopy &Mosquitoes &Severe Malaria Bill Brieger | 30 Sep 2020

Malaria News Today 2020-09-30: Diagnostics, Mosquito Genes and Neutrophils

Mosquito populations vary across nations and can be spurred by change in land use and deforestation as seen in Madagascar. Urine and saliva have potential in diagnostics but have lower sensitivity than blood tests. Not all insects have similar genes, and mosquitoes evolved a different gene to handle body segmentation. The DHS Program has released recent Malaria Indicator Surveys for Ghana and Uganda, but indicators are below targets. The emerging roles for neutrophils in malaria will be discussed at a webinar. Finally cost-effectiveness issues around RDTs is noted. More information can be obtained via the hyperlinks.

Variation in Anopheles distribution and predictors of malaria infection risk across regions of Madagascar

Deforestation and land use change is widespread in Madagascar, altering local ecosystems and creating opportunities for disease vectors, such as the Anopheles mosquito, to proliferate and more easily reach vulnerable, rural populations. Knowledge of risk factors associated with malaria infections is growing globally, but these associations remain understudied across Madagascar’s diverse ecosystems experiencing rapid environmental change. This study aims to uncover socioeconomic, demographic, and ecological risk factors for malaria infection across regions through analysis of a large, cross-sectional dataset.

The presence of aquatic agriculture (both within and surrounding communities) is the strongest predictive factor of habitats containing Anopheles larvae across all regions. Ecological and socioeconomic risk factors for malaria infection vary dramatically across study regions and range in their complexity. Risk factors for malaria transmission differ dramatically across regions of Madagascar. These results may help stratifying current malaria control efforts in Madagascar beyond the scope of existing interventions.

Evaluating the potential of using urine and saliva specimens for malaria diagnosis in suspected patients in Ghana

This study aimed at detecting PfHRP2 and pLDH malaria antigens in urine and salivary specimens of suspected malaria patients using RDT kits, and identifying factors influencing the detection of these antigens. Malaria rapid test kit (SD Bioline RDT kit) was used to detect malaria antigens, PfHRP2 and pLDH, in blood, urine and saliva samples received from patients suspected of malaria. Subsequently, malaria parasitaemia was determined.

A total of 706 suspected malaria patients provided all three specimens. Prevalence of malaria by microscopy and RDT was 44.2% and 53.9%, respectively. Compared to blood, the sensitivities of urine and saliva were 35.2% and 57.0% respectively. Haemoglobin concentration?<?9.9 g/dL, body temperature?>?38.7 °C and occult blood influenced the detection of malaria antigens in both urine and saliva. Furthermore, the antigens were not detected in urine and saliva when parasitaemia was?<?60,000 parasites/µL and?<?40,000 parasites/µL, respectively.

Saliva, with or without blood contamination, was found to be more efficient that urine samples. Therefore these non-blood specimens have the potential to be used as non-invasive samples for malaria diagnosis. However, this approach is useful in severe to moderate anaemia, hyperthermia, parasitaemia?>?60,000 parasites/µL and samples contaminated with blood.

Mosquitos lost an essential gene for body segmentation with no ill effects

University of Maryland entomologists discovered that a gene critical for survival in other insects is missing in mosquitoes—the gene responsible for properly arranging the insects’ segmented bodies. The researchers also found that a related gene evolved to take over the missing gene’s job. Although laboratory studies have shown that similar genes can be engineered to substitute for one another, this is the first time that scientists identified a gene that naturally evolved to perform the same critical function as a related gene long after the two genes diverged down different evolutionary paths.

The work emphasizes the importance of caution in genetic studies that use model animals to make conclusions across different species. It also points to a new potential avenue for research into highly targeted mosquito control strategies. The research study was published in the September 30, 2020, issue of the journal Communications Biology. “Every single arthropod has a segmented body plan. And you would think it develops the same way in all of them. But what we found is that it doesn’t,” said Alys Jarvela. “That means different genes probably regulate male fertility in mosquitoes, and they might be unique to the mosquito, which could potentially provide a powerful avenue for controlling mosquitoes without harming other insects such as butterflies and bees,” Jarvela said.

Two New Malaria Indicator Surveys Available

Ghana 2019 MIS/DHS Infographic. Malaria prevalence going down from 27% in 2014 to 14% in 2019. Still below target in terms of ITN coverage of and in households.

Uganda 2018-19 MIS/DHS Infographic.  Wide regional variation in malaria prevalence from 1-5% in the southwest to 34% in the northeast. ITN use by children and pregnant women below 2/3rds, while only 2/5 pregnant women got 3 doses of IPT.

Emerging Roles for Neutrophils in Malaria

Aubrey Cunnington and an interdisciplinary translational research group studying host-pathogen interactions in severe infections, focussing on malaria in particular. See for example,  “A More Granular View of Neutrophils in Malaria

Neutrophils are abundant innate immune cells with crucial roles in immunity and vascular inflammation. Recent evidence indicates that neutrophils have a dual role in malaria, contributing to both pathogenesis and control of Plasmodium. We discuss emerging mechanisms behind these opposing functions and identify key outstanding questions.

Cost-effectiveness analysis of malaria rapid diagnostic test in the elimination setting

As more and more countries approaching the goal of malaria elimination, malaria rapid diagnostic tests (RDT) was recomended to be a diagnostic strategy to achieve and maintain the statute of malaria free, as it’s less requirements on equipment and expertise than microscopic examination. But there are very few economic evaluations to confirm whether RDT was cost-effective in the setting of malaria elimination. This research aimed to offer evidence for helping decision making on malaria diagnosis strategy.

The results showed that RDT strategy was the most effective (245 cases) but also the most costly (United States Dollar [USD] 4.47 million) compared to using microscopy alone (238 cases, USD 3.63 million), and RDT followed by microscopy (221 cases, USD 2.75 million). There was no strategy dominated. One-way sensitivity analysis reflected that the result was sensitive to the change in labor cost and two-way sensitivity analysis indicated that the result was not sensitive to the proportion of falciparum malaria. The result of Monte Carlo simulation showed that RDT strategy had higher effects and higher cost than other strategies with a high probability. Compared to microscopy and RDT followed by microscopy, RDT strategy had higher effects and higher cost in the setting of malaria elimination.

Diagnosis &Elimination &Funding &IPTp &ITNs &Journalists/Media &Malaria in Pregnancy &Migration &Zero Malaria Bill Brieger | 26 Sep 2020

Malaria News Today 2020-09-26: supporting and strengthening malaria programs

Today’s selection of abstracts and news looks at the role of the media in supporting malaria programs, mass treatment to prevent Imported malaria, problems managing malaria in pregnancy services, malaria research in Mali and health systems strengthening to support malaria control in Guinea. Follow links to read mor details.

GHS calls for media support to eradicate malaria

The media has a role in supporting malaria programs

The Ghana Health Service (GHS) has called on journalists to support the Service to deliver integrated health package through accurate messages towards malaria eradication in the country.“Also, we need your support to set malaria as a national development agenda. This will drive advocacy for political will, increase partnership, availability and accessibility of effective tool for prevention, diagnoses and treatment of malaria in all the vulnerable populations.”

Dr Anthony Adofo Ofosu, the Deputy Director General, GHS, said this at the launch of “Zero malaria starts with me” campaign in Accra.  The launch coincided with a sensitisation programme by the African Media and Malaria Research Network (AMMRN), the National Malaria Control Programme and the Speak Up African Organisation. The Deputy Director General said “It is the belief of the GHS that with effective engagement…we will be able to eradicate malaria from the country in the near future.”

Mass radical treatment of a group of foreign workers to mitigate the risk of re-establishment of malaria in Sri Lanka

Following malaria elimination, Sri Lanka was free from indigenous transmission for six consecutive years, until the first introduced case was reported in December 2018. The source of transmission (index case) was a member of a group of 32 migrant workers from India and the location of transmission was their residence reporting a high prevalence of the primary vector for malaria. Despite extensive vector control the situation was highly susceptible to onward transmission if another of the group developed malaria. Therefore, Mass Radical Treatment (MRT) of the group of workers for Plasmodium vivax malaria was undertaken to mitigate this risk.

The workers were screened for malaria by microscopy and RDT, their haemoglobin level assessed, and tested for Glucose 6 phosphate dehydrogenase deficiency (G6PD) using the Care Start RDT and Brewers test prior to treatment with chloroquine (CQ) 25 mg/kg body weight (over three days) and primaquine (PQ, based on G6PD test results) (0.25 mg/kg/day bodyweight for 14 days) following informed consent. All were monitored for adverse events. None of the foreign workers were parasitaemic at baseline screening.

Mass treatment may be an option in prevention of reintroduction settings for groups of migrants who are likely to be carrying latent malaria infections, and resident in areas of high receptivity. However, in the case of Plasmodium vivax and Plasmodium ovale, a more reliable and affordable point-of-care test for G6PD activity would be required. Most countries which are eliminating malaria now are in the tropical zone and face considerable and similar risks of malaria re-introduction due to massive labour migration between them and neighbouring countries. Regional elimination of malaria should be the focus of global strategy if malaria elimination from countries is to be worthwhile and sustainable.

Managing intermittent preventive treatment of malaria in pregnancy challenges: an ethnographic study of two Ghanaian administrative regions

Malaria in pregnancy (MiP) is an important public health problem across sub-Saharan Africa. The package of measures for its control in Ghana in the last 20 years include regular use of long-lasting insecticide-treated bed nets (LLINs), directly-observed administration (DOT) of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and prompt and effective case management of MiP. Unfortunately, Ghana like other sub-Saharan African countries did not achieve the reset Abuja targets of 100% of pregnant women having access to IPTp and 100% using LLINs by 2015.

This ethnographic study explored how healthcare managers dealt with existing MiP policy implementation challenges and the consequences on IPTp-SP uptake and access to maternal healthcare. Healthcare managers addressed frequent stock-outs of malaria programme drugs and supplies from the National Malaria Control Programme and delayed reimbursement from the NHIS, by instituting co-payment, rationing and prescribing drugs for women to buy from private pharmacies.

Some clients did not receive the recommended 5?+?doses of SP, others did not obtain LLINs early and some did not obtain treatment for MiP. Healthcare providers felt frustrated whenever they could not provide comprehensive care to women who could not afford comprehensive maternal and MiP care. For Ghana to achieve her goal of controlling MiP, the Ministry of Health and other supporting institutions need to ensure prompt reimbursement of funds, regular supply of programme drugs and medical supplies to public, faith-based and private health facilities.

Malaria prevention program continuation in Guinea

CRS Guinea is the Principal Recipient (PR) in Malaria prevention program continuation grant by the Global Fund for the new cycle of funding (NFM) (January 2021-December 2023). Community health is a top priority of the Ministry of Health as a primary strategy to increase accessibility and coverage to basic health services. Under the new Global Fund grant, the community health component will be expanded to six districts, in addition to two pilot districts, Kindia and Telimele. CRS will also support coordination with other donors, including World Bank, UNICEF, Gavi, European Union and the Guinea Ministry of Health to implement the national community health strategy in 12 health districts supported by Global Fund malaria project.

The United States and Mali Celebrate 60 Years of Friendship and Partnership

Thirty years ago, our National Institutes of Health created a Malaria Research and Training Center, which is now a component of the International Center for Excellence in Research in Mali. Until today, it serves as a reference center with over 700 Malian scientists and support staff who work on malaria and other infectious diseases. Together, we have dropped malaria prevalence rates in Mali by an astounding 60 percent since 2012.

 

Artesunate &Children &Diagnosis &Elimination &Plasmodium/Parasite &Private Sector &Resistance &Surveillance Bill Brieger | 25 Sep 2020

Malaria News Today 2020-09-25: Testing, Surveillance, Elimination

Differentiating malaria parasite species is something science can do today, but in the 1800s the debate was over what actually caused the disease.  This ability to test and diagnose gives us an important surveillance tool, the 3Ts. News from Ghana is that malaria deaths are reducing, and Guatemala is focusing on elimination. Read more at the links in each section.

Wyss Researchers Develop Malaria Diagnostic Procedure Capable of Differentiating Malaria Species

Researchers at Harvard’s Wyss Institute have developed a new malaria diagnostic test that efficiently detects and can distinguish between species of malaria parasites,
the new procedure significantly improves upon current diagnostic methods, which fail to differentiate between types of malaria. Procedures that only identify Plasmodium falciparum can lead to severe consequences for patients, since other types of malaria are resilient to therapies designed to treat Plasmodium falciparum because they enter a dormant stage in the human liver.

These genes help explain how malaria parasites survive treatment with common drug.

The essential malaria drug artemisinin acts like a “ticking time bomb” in parasite cells—but in the half a century since the drug was introduced, malaria-causing parasites have slowly grown less and less susceptible to the treatment, threatening attempts at global control over the disease.

In a paper published September 23 in Nature Communications, Whitehead Institute Member Sebastian Lourido and colleagues use genome screening techniques in the related parasite Toxoplasma gondii (T. gondii) to identify genes that affect the parasites’ susceptibility to artemisinin. Two genes stood out in the screen: one that makes the drug more lethal, and another that helps the parasite survive the treatment…

Test, Treat, and Track: Strengthening Malaria Response Capabilities in Sierra Leone

A public-private partnership in Sierra Leone aimed to build capacity for testing, treating, and tracking malaria. The post notes the “public-private partnership in Sierra Leone was a collaboration between USAID’s Human Resources for Health in 2030 (HRH2030) program; the U.S. President’s Malaria Initiative (PMI), the Global Fund to Fight AIDS, Tuberculosis and Malaria; the Pharmacy Consultancy of Sierra Leone; and the Sierra Leone National Malaria Control Program”.

NMCP partnered with pharmacies to strengthen their malaria case management capabilities. Anitta and her colleague Brenda Stafford, a trained pharmacist and Procurement and Supply Management officer, led the initiative, going pharmacy-to-pharmacy to train staff on the NMCP’s “Three T” approach: Test, Treat, and Track.

To address the first T, private pharmacies were given free malaria rapid diagnostic tests. According to 2016 data, only half of children under-five with fever received appropriate malaria testing. For the second T, the pharmacists were trained on malaria prevention, treating patients with uncomplicated malaria, and referring patients with severe malaria to health facilities. As for the last T, tracking malaria test results is key in forecasting the spread of disease. NMCP provided pharmacies with two forms that track results: a registry form to track patient information and a summary form which aggregates that into monthly data reports

Miasma War over cause of malaria was heated

Nicole Layton of the Chowan Herald reported that in the 1850s, two North Carolina doctors had a heated and protracted battle over the cause of malaria in the state. This Miasma War is so famous. So what the heck is Miasma? Those fans of Charles Dickens can tell you that at one point miasmas were thought to be the main vector for disease transmission.

During Dickens’ time in London the air was very foul and rather visible because of wood and coal and it smelled bad due to the lack of indoor plumbing. It was thought that this foul air was the cause of disease. Because our part of North Carolina had a lot of rotting vegetation and swamps there was certainly foul air about and very noticeable illness. So the general thought was that malaria was a result of this bad air.

Escuintla, Guatemala: Clinton Health Access Initiative (CHAI)

CHAI’s Guatemala Malaria Team is supporting the Ministry of Health’s National Malaria Program by providing technical assistance and supporting programmatic planning, execution, monitoring and evaluation of effective interventions in the department of Escuintla in southern Guatemala. Over the past five years, CHAI has engaged in the country and helped them make meaningful steps towards orienting their national strategic plans and systems towards the historical goal of malaria elimination.

CHAI’s Guatemala team works in close coordination with the Ministry of Health and other international partners to design, plan, execute and evaluate the impact of the country´s elimination-focused interventions in Escuintla.

Ghana: Malaria deaths in children under five reduce

Ghana has recorded a reduction in malaria deaths in children under five by 83 per cent over the last eight years, the National Malaria Control Programme (NMCP) has said. The rate of malaria-related deaths reduced from 0.6 per cent in 2012 to 0.1 per cent in 2019, showing significant inroads in malaria-related deaths among children. Malaria-related deaths of all ages also reduced by 2,799 in 2012 to 333 by end of 2019, representing an 88 per cent reduction.

Agriculture &Counterfeit Drugs &Dengue &Diagnosis &Elimination &Environment &Floods &Irrigation &Mosquitoes &Severe Malaria &Surveillance &water Bill Brieger | 24 Sep 2020

Malaria News Today 2020-09-23/24

Today the issue of water is important for malaria mosquito propagation, both in irrigation and flooding. Artificial skin enables testing of mosquito biting. Fake medicines for malaria and other conditions threaten Africa’s health. Archived RDTs can aid surveillance. Finally there is concern for co-infection with both malaria and dengue leading to severe disease. Follow links below to read details.

Impact of sugarcane irrigation on malaria vector Anopheles mosquito fauna, abundance and seasonality in Arjo-Didessa, Ethiopia

Despite extensive irrigation development in Ethiopia, limited studies assessed the impact of irrigation on malaria vector mosquito composition, abundance and seasonality. This study aimed to evaluate the impact of sugarcane irrigation on species composition, abundance and seasonality of malaria vectors. Adult Anopheles mosquitoes were collected using CDC light traps from three irrigated and three non-irrigated clusters in and around Arjo-Didessa sugarcane irrigation scheme in southwestern Ethiopia.

Overall, 2108 female Anopheles mosquitoes comprising of six species were collected. The ongoing sugarcane irrigation activities in Arjo-Didessa created conditions suitable for malaria transmitting Anopheles species diversity and abundance. This could drive malaria transmission in Arjo-Didessa and its environs in both dry and wet seasons. Currently practiced malaria vector interventions need to be strengthened by including larval source management to reduce vector abundance in the irrigated areas.

Prevalence of and risk factors for severe malaria caused by Plasmodium and dengue virus co-infection

A systematic review and meta-analysis examined co-infection with both Plasmodium and dengue virus (DENV) infectious species could have serious and fatal outcomes if left undiagnosed and without timely treatment. The present study aimed to determine the pooled prevalence estimate of severe malaria among patients with co-infection, the risk of severe diseases due to co-infection, and to describe the complications of severe malaria and severe dengue among patients with co-infection. Relevant studies published between databases between 12 September 1970 and 22 May 2020 were identified and retrieved.

The present study found that there was a high prevalence of severe malaria among patients with Plasmodium and DENV co-infection. Physicians in endemic areas where these two diseases overlap should recognize that patients with this co-infection can develop either severe malaria or severe dengue with bleeding complications, but a greater risk of developing severe dengue than severe malaria was noted in patients with this co-infection.

South Sudan: Flooding deepens a humanitarian crisis in Pibor area

Today, however, the Pibor River has swelled to make parts of the town inaccessible and is threatening the clinic. Many neighborhoods cannot be reached by foot, and a local ferry is too expensive for many who live in the area. A mobile MSF team is providing medical care in hard-to-reach areas. “Our focus is now on malaria, measles and flooding,” said Josh Rosenstein, MSF deputy head of mission. “Today we are reaching out to the community through our daily mobile clinics, treating the most severe illnesses. We’re also implementing our flood contingency plan, which includes building additional flood defenses around the clinic to ensure we can continue to provide medical services, as the water level is rising at an alarming speed.”

Stratifying malaria receptivity in Bangladesh using archived rapid diagnostic tests

Surveillance of low-density infections and of exposure to vectors is crucial to understand where malaria elimination might be feasible, and where the risk of outbreaks is high. Archived rapid diagnostic tests (RDTs), used by national malaria control and elimination programs for clinical diagnosis, present a valuable, yet rarely used resource for in-depth studies on malaria epidemiology. 1022 RDTs from two sub-Districts in Bangladesh (Alikadam and Kamalganj) were screened by qPCR for low-density Plasmodium falciparum and Plasmodium vivax infections, and by ELISA for Anopheles salivary gland antibodies as a marker for exposure to vectors.

Concordance between RDT and qPCR was moderate. qPCR detected 31/1022 infections compared to 36/1022 diagnosed by RDT. Exposure to Anopheles was significantly higher in Kamalganj despite low transmission, which could be explained by low bed net use. Archived RDTs present a valuable source of antibodies for serological studies on exposure to vectors. In contrast, the benefit of screening archived RDTs to obtain a better estimate of clinical case numbers is moderate. Kamalganj could be prone to outbreaks.

New tool mimics human skin to allow detailed study of mosquito biting

eLife: Researchers develop a human skin mimic to study mosquito biting in high resolution without using humans as ‘bait.’ The tool, which uses an artificial blood meal and a surface that mimics human skin, will provide detailed understanding of blood feeding without using human subjects as bait. It can also fit conveniently into a backpack, allowing the study of mosquitoes in laboratory and natural environments.

Blood feeding is essential for mosquitoes to reproduce, but it is during blood feeds on human hosts that they pass on pathogens such as malaria. It consists of a bite ‘substrate’ – a transparent, temperature-controlled surface that mimics body temperature to attract mosquitoes. An artificial meal is applied on top of this and covered with a commonly used membrane that mosquitoes can pierce. The meal resembles blood, allowing mosquitoes to engorge and increase their weight by two to threefold. This bite substrate is then placed in a transparent cage, and an external camera records the mosquitoes’ behaviour. The team tested biteOscope with four medically important species of mosquito.

Counterfeiting of Fake Drugs in Africa: current situation, causes and countermeasures

The more desirable a product is the higher the tendency to replicate it and meet that parcel of consumers that want to join the trend but cannot pay the price. Profit is one of the many reasons that make counterfeit an attractive business for many.  Africa, unfortunately but not surprisingly, is one of the most affected continents, comprehensible since its markets have become a huge target for second generation goods, with a major focus on pharmaceutical drugs.

The World Health Organization (hereinafter, WHO) stated that 42% of all fake medicine reported to them between the years of 2013 and 2017 was linked to the African continent and we expect that these numbers fall short of reality. Africa is seriously affected by it and one clear example is the anti-malarial medication. Anti-malarials and antibiotics are amongst the most commonly reported as fake or substandard medical products.

Anemia &Culture &Diagnosis &immune system &Indigenous Medicine &Malaria in Pregnancy &Mosquitoes &Self-Treatment &Social/Cultural &Surveillance Bill Brieger | 19 Sep 2020

Malaria News Today 2020-09-18/19

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.

Climate &COVID-19 &Dengue &Diagnosis &Environment &Invest in Malaria Control &Mapping &mHealth &Migration &Mosquitoes &Nomadic People &Surveillance Bill Brieger | 11 Sep 2020

Malaria News Today 2020-09-11

Today’s news and abstracts look at a variety of issues ranging from overall malaria funding funding needs to the effect of climate change on different types of mosquitoes and the diseases they carry (e.g. malaria vs dengue). We also examine the need for surveillance among nomadic groups and the use of cell phones in a saliva based malaria testing system. Please click the links below to read more on each subject.

Rwanda: Government Needs U.S.$70 Million to Fill Malaria Financing Gap

By Nasra Bishumba: The Government needs $73 million to bridge the funding in the funds needed to fight malaria between 2020 and 2024, The New Times can reveal. The Rwanda National Strategic Plan 2020-2024 to fight malaria drawn up in June this year indicates that although the implementation requires Rwf295bn ($280 million), the government already has funding commitment to the tune of $206.8m (equivalent to 74 per cent).

According to the strategic plan, a copy of which The New Times has seen, this leaves a gap of $73m which it hopes to mobilize from different sources. With these funds, the government is seeking to protect at least 85 per cent of the population with preventive interventions and to work towards promptly testing and treating suspected malaria cases by 2024. To achieve this, the biggest chunk of the funds will be invested in malaria prevention to a tune of $186m, an equivalent of 66 per cent of the entire budget.

Climate Change May Shift Risks of Mosquito-borne Diseases

By Asher Jones: More dengue, less malaria. That may be the future in parts of Africa on a warming planet, depending on where you live. New research says it’s all about which mosquitoes will thrive. And the methods to control one don’t necessarily work on the other.

The mosquito that spreads malaria prefers relatively cool temperatures of 25 degrees Celsius (77 degrees Fahrenheit). The dengue mosquito does best at 29 degrees Celsius (84.2 degrees Fahrenheit). Because of this difference in optimal temperatures, “We would actually predict that climate change might have opposing effects [on disease transmission],” said Erin Mordecai, assistant professor of biology at Stanford University and lead author on the study. “Climate change might make it less suitable for malaria to be transmitted but more suitable for dengue to be transmitted.”

Africa’s Nomadic Pastoralists and Their Animals Are an Invisible Frontier in Pandemic Surveillance

@ASTMH The effects of COVID-19 have gone undocumented in nomadic pastoralist communities across Africa, which are largely invisible to health surveillance systems despite the fact that they are of key significance in the setting of emerging infectious disease. We expose these landscapes as a “blind spot” in global health surveillance, elaborate on the ways in which current health surveillance infrastructure is ill-equipped to capture pastoralist populations and the animals with which they coexist, and highlight the consequential risks of inadequate surveillance among pastoralists and their livestock to global health. As a platform for further dialogue, we present concrete solutions to address this gap.

Mobile phone-based saliva test wins NIH prize

Cornell researchers’ concept for a quick, non-invasive, mobile phone-based system to detect infectious diseases, inflammation and nutritional deficiencies in saliva was awarded a $100,000 National Institutes of Health Technology Accelerator Challenge prize. The NIH’s prize challenge encourages the development of new, non-invasive diagnostic technologies important for global health. For the group’s saliva-based test, a small 3D-printed adapter is clipped to a mobile phone and synced with a mobile app. The app uses the phone’s camera to image test strips to detect malaria, iron deficiency and inflammation, with results in under 15 minutes.

The proposal builds on the FeverPhone and NutriPhone platforms developed by the team at Cornell’s Institute for Nutritional Sciences, Global Health and Technology (INSiGHT). The technologies, funded by the NIH and the National Science Foundation, evaluate infections and nutritional status using blood. According to Mehta, technologies using salivary biomarkers could revolutionize how conditions such as malaria and iron deficiency are identified and addressed, especially in settings where access to primary health care and traditional, laboratory-based tests is limited.

Monsoon infections: How to tell the difference between dengue and malaria? Watch out for these symptoms

While both diseases are mosquito-borne and cause similar symptoms such as fever, joint/muscle pain, headaches, and fatigue, some differences between their symptoms can help you identify the specific infections. Unique symptoms of Malaria: Stomach problems such as vomiting, Diarrhoea, Dry cough, Shivering, Spleen enlargement Unique symptoms of Dengue: Pain behind the eyes, Swollen glands, Rashes

Next Page »