Category Archives: Severe Malaria

The Heart of the Malaria Problem

Case Management, Severe Malaria

February is Heart Month in some countries. This is a good time to explore how malaria affects the heart and cardiovascular health.

In 1946 Howard Sprague observed that although “malaria is a disease from which no organ or tissue is exempt, this paper is concerned with its influence upon the circulation, and more particularly upon the heart itself.” He then outlined four ways by which this influence happens:

  1. its chronic and recurrent nature
  2. the systemic toxemia of the paroxysm
  3. the profound anemia produced by hemolysis and suppression of hemopoiesis
  4. the occlusion of capillaries and arterioles of the myocardium

Since that time other researchers have elaborated on malaria and the cardiovascular system.

Mishra et al. raise a concern that, “The role of the heart in severe malaria has not received due attention.” They point out the following:

  • hypotension, shock and circulatory collapse observed in severe malaria patients
  • raised cardiac enzymes in complicated malaria
  • compromised microcirculation and lactic acidosis as well as excessive production of pro-inflammatory cytokines
  • Intravascular fluid depletion associated with severe malaria leading to impaired microcirculation … among others

They conclude that “Sudden cardiac deaths can also occur due to cardiac involvement,” but worry that, “It is not feasible to assess the cardiac indices in resource poor settings.”

A study by Ray and co-researchers indicated “involvement of cardiovascular system in severe malaria as evidenced from ECG and echocardiography. The study also revealed that cardiovascular instabilities are common in falciparum malaria, but can also be observed in vivax malaria.” A fatal case of imported malaria where the sole finding revealed at the postmortem evaluation was an acute lymphocytic myocarditis with myocardiolysis was described by Costenaro and colleagues.

In another example, Onwuamaegbu, Henein, and Coats reviewed the potential role of malaria in chronic and severe malaria and the connection to chronic heart failure. They concluded that, “Our review of the literature suggests that there are significant similarities in the cachexia seen in CHF and that of malaria, especially as related to the effects of muscle mass and immunology.” Clinical manifestations in P. falciparum malaria also include reduced cardiac output as was reported in an imported case of malaria by Johanna Herr and co-workers.

Marrelli and Brotto note that, “Sequestration of red blood cells, increased levels of serum creatine kinase and reduced muscle content of essential contractile proteins are some of the potential biomarkers of the damage levels of skeletal and cardiac muscles.” They explain that, “These biomarkers might be useful for prevention of complications and determining the effectiveness of interventions designed to protect cardiac and skeletal muscles from malaria-induced damage.”

Not just malaria as a disease is involved, but also the medicines used to treat it. Ngouesse and colleagues draw attention to antimalarial drugs with cardiovascular side effects. They draw particular attention to the dangers of halofantrine, quinine and quinidine, but also note mild and/or transient effects of other antimalarials.

Guidelines exist for proper and prompt malaria case management, especially protocols for caring for patients with severe malaria. These and the medicines required must be more readily available to front line health staff. And of course is we are more diligent in preventing malaria through long lasting insecticide-treated nets and other measures, our worries about severe malaria and CVD complications will reduce.

Severe malaria case management practices in selected states in Nigeria: Need for urgent intervention

Severe Malaria, Treatment

At the recently concluded American Society of Tropical Medicine and Hygiene 2014 Annual Meeting, USAID’s MAPS Project presented a poster on severe malaria in Nigeria. The authors, Yetunde Oke, Banji Ipadeola, Bolatito Aiyenigba, Grace Nwankwo, Justice Adaji, Olatunde Olotu, Aniefiok Akpasa, and Abba Umar, share their findings below.

maps logoSevere malaria is a life threatening medical condition that requires emergency interventions including prompt and effective treatment to prevent death (WHO 2000). The AQUAMAT* study showed a relative reduction in mortality of 22.5% with use of parenteral artesunate compared to quinine in the management of severe P. falciparum malaria and the Nigeria national policy on malaria diagnosis and treatment has been revised based on this evidence.

However, implementation of this guideline is still a challenge. The goal of this study was to determine baseline capacity and management practices for severe malaria in selected secondary health facilities in Nigeria with the aim of designing interventions to address specific gaps identified.

A cross?sectional study was conducted to assess twenty?four secondary public health facilities in three states (Benue, Kogi and Oyo States) in Nigeria in August 2013. Data on the capacity of health care providers; malaria services provided at different service delivery points (three months preceding the survey).

Medical supplies were collected using modified WHO severe malaria assessment tools. Data  entry was done  using the SPSS software programme and analysis done with STATA version 10.0.

Prev Severe MalTotal number of confirmed malaria cases reported in the three states over the three months preceding the assessment was 18, 695 and diagnosis of severe malaria was made in 8.6% of the total malaria cases. Out of the severe malaria cases, 75.9% were discharged, 3.8% referred and 1.5% died.

Fifty per cent of the health care providers had attended training on malaria case management 12 months preceding the survey. The majority of providers managed severe malaria with injectable artemether (45.8%), quinine (37.5%) compared with artesunate (29.2%).

Routine antimalarialsMost of the health facilities (95.8%) practiced parasite-based diagnosis of malaria but only (29.2%) monitored the parasite clearance of patients with severe malaria. 70% of the facilities did not have basic supplies for ancillary management of severe malaria. 66.7% and 30% of the health facilities experienced stock?out of parenteral artesunate and parenteral  quinine respectively  in the previous three months.

Health system strengthening with emphasis on capacity building of health care providers, medical commodity security and improvement in supportive/ancillary management of severe malaria is needed to reduce the mortality attributable to severe malaria.

Sunday Symposium #176 at TropMed2013 Malaria: Biology and Pathogenesis – Human Responses to falciparum

Plasmodium/Parasite, Severe Malaria

AnnualMeetinggraphicOn this final day of the American Society of Tropical Medicine and Hygiene’s 62nd Annual Conference, there is a featured symposium on Malaria: Biology and Pathogenesis – Human Responses to falciparum. Presentations are listed below with links to the abstracts online.

Demonstration of enhanced strain-specific Plasmodium falciparum multifunctional T cell cytokine expression among Malian children immunized with the FMP2.1/AS02A vaccine by Shawna F. Graves et al.

The Study suggests that AMA1 vaccination induced an AMA1-specific CD4+ response; however, recognition of the vaccine antigen is not dependent upon c1L alone. In summary, AMA1-specific T cell cytokine expression was notably increased in children vaccinated with an AMA1-based vaccine compared to rabies. The possible role of CD4+ TNF-?+IL-2+-expressing T cells in vaccine-induced strain-specific protection against clinical malaria requires further exploration.

Fatal Pediatric Cerebral Malaria is Associated with Intravascular Inflammation and Coagulation that is Exacerbated by HIV-1 Co-infection by Sarah Hochman and colleagues.

We hypothesize that the intravascular inflammation and coagulation seen in CM autopsies contribute to the pathogenesis of pediatric CM and that dysregulation of these processes in HIV infection contribute to CM mortality.

Immune responses of rhesus monkeys to a self-assembling protein nanoparticle (SAPN) vaccine displaying Plasmodium falciparum CSP B- and T-cell epitopes by David E. Lanar and co-researchers.

We have previously studied in mice the immune responses induced against Plasmodium falciparum circumsporozoite protein (PfCSP) epitopes using a self-assembling protein nanoparticle (SAPN) platform. In conclusion, a PfCSP-KMY-SAPN vaccine for malaria was safe and immunogenic in rhesus monkeys. Immune responses to the vaccine were greatly enhanced if the nanoparticle was formulated with the adjuvant GLA-SE.

Non-invasive Pulse Oximetry to Predict Mortality in African Children with Malaria by Andrea L. Conroy et al.

The mortality rate for children admitted with malaria was 3.1%. We evaluated whether non-invasive pulse oximetry would predict disease outcome in malaria and compared the findings to venous lactate, an established prognostic marker in malaria. These data suggest that pulse oximetry alongside assessment of venous lactate may be useful in the triage and treatment of children with severe malaria. Additional advantages in pulse oximetry are low operating costs and real-time patient monitoring.

Placental malaria induces excessive vasculogenesis by  Tara C. Bracken and colleagues.

Placental malaria (PM) results from sequestration of Plasmdium falciparum-infected erythrocytes and the resulting inflammatory responses in the maternal placental blood space. PM induces maternal anemia, preterm birth, low birth weight, or stillbirth, especially in primigravidae. The active/active chronic group had a significantly higher percentage of excessive vasculogenesis.

Retinal microvascular dysfunction in pediatric cerebral malaria is associated with death and neurological sequelae by Ian J. MacCormick and co-authors.

Our results suggest that central nervous system ischemia and leakage across blood-tissue barriers may be important contributors to the severity of pediatric Cerebral Malaria.

Are non-communicable diseases actually communicable?

Chronic/NCDs, Epidemiology, Mortality, Severe Malaria

Much of the discussion around global health and post-Millennium Development Goals focuses on non-communicable diseases (NCDs) including cardiovascular problems, diabetes, cancers and the the like.  While it is important to recognize that low income nations are not plagued with both communicable and non-communicable diseases, we do not want the greater focus on NCDs in richer countries to overshadow the problems of malaria, pneumonia, TB, diarrhea and other child killers in poorer countries.

dscn7742-chw-flipchart.jpgA major reason for us not to lose focus on communicable diseases was recently reported from the Wellcome Trust on research they have supported in Malawi. The researchers found that the malaria parasite, Plasmodium falciparum, is able to “cause inflammation in blood vessel walls, making them more sticky so that the infected red blood cells can cling to the sides. Being able to stick to the blood vessels in vital organs allows the parasite to hide away from the immune system, a process called sequestration. When it occurs in the brain it causes a more severe form of the disease called cerebral malaria, associated with seizures, coma and sometimes death.”

The researchers also surmised that if this complication does not kill people in childhood, the damage to blood vessel walls can have more long lasting effects. In particular they noted that, “Chronic changes to the blood vessels like these could an important contributing factor to cardiovascular disease later in life.”

The link between malaria and Endemic Burkitt lymphoma (eBL) continues to be explored. Recently adding to this long history of eBL research, Peter Aka and colleagues reported that. “Anti–HRP-II (Plasmodium falciparum histidine-rich protein-II) antibodies suggest that recent malaria infection triggers the onset of eBL.”

In a review of intrauterine growth retardation (IUGR) Demicheva and Crispi observed that, “Several clinical and experimental studies showed that IUGR fetuses present signs of cardiac dysfunction in utero that persist postnatally and may condition higher cardiovascular risk later in life.” In endemic regions, malaria in pregnancy is a major cause of IUGR and thus low birth weight.

Preventing malaria therefore saves lives now and in the future. Ignoring malaria now adds greater burdens to the health system and national productivity tomorrow. We need to maintain our investments in malaria both globally and in and by endemic countries themselves.

Disabilities – the role of malaria

Severe Malaria

sotwc-2013-unicef_reports_reportcover_ena.jpgUNICEF’s 2013 State of the World’s Children focuses on “Children with Disabilities.”  Some attention is paid to the role of communicable or infectious disease in the cause of disabilities and the need for children with disabilities to benefit from disease control services, just like any other child.

Of particular focus in the realm of infectious disease is recognition that, “… immunization is an important means of pre-empting diseases that lead to disabilities.” The Report goes on to explain for example, that, “More children than ever before are being reached. One consequence has been that the incidence of polio – which can lead to permanent muscle paralysis – fell from more than 350,000 cases in 1988 to 221 cases in 2012.”

Malaria as an infectious disease continues to exert a disabling effect on children in endemic countries. The Report does present a case study of children who spent several years in a residential home for children with mental disabilities in the Republic of Moldova, but it is also important to recognize that malaria and other infectious diseases can lead to such problems.

In reporting on neurological disease in Sub-Saharan Africa, Donald Silberberg and Elly Katabira explained that, “In addition to the hundreds of thousands of children who die each year from cerebral malaria, many more survive (often repeated attacks) and develop sequelae that have yet to be quantified. These include cognitive disorders and epilepsy.”

Likewise Ngoungou and colleagues after studying children with cerebral malaria in Mali found persistent neurological sequelae including, “ headaches, mental retardation, speech delay, bucco-facial dyspraxia, diplegia and frontal syndrome (one case each), dystonia (two cases), epilepsy (five cases) and behavior and attention disorders (15 cases).”

Immunization is of course a major tool in preventing disability, but we also need to examine the role other disease control efforts can play on preventing disability. Also as mentioned in the case of immunization above, we also need to ensure that all children with any kind of disability in a malaria endemic area promptly receive all necessary treatment and preventive interventions.

Epilepsy – a long term consequence of severe malaria

Severe Malaria

When calculating the burden of malaria, we often forget the longer term disabilities that persist after an acute episode. Specifically, Kariuki and co-researchers highlight that, “Falciparum malaria is an important cause of acute symptomatic seizures in children admitted to hospitals in sub-Saharan Africa, and these seizures are associated with neurological disabilities and epilepsy.”
In a new review in Neurology, Ngugi and colleagues report that …

“Our estimates suggest that the incidence of epilepsy in LMIC (low and middle income countries) is approximately twice that of HIC (high income countries) … The cause of the higher incidence in resource-poor compared to industrialized countries is likely to be multifactorial. The higher incidence of head trauma and of infections and infestations of the CNS (central nervous system) such as malaria, neurocysticercosis, and invasive bacterial infections may be important causes.”

dscn9102sm.jpgPreventing malaria or treating malaria in a very timely manner is a crucial step in reducing the long term burden of disease in individuals and countries. Kariuki et al. note a challenge: “… it is difficult to determine the proportion of seizures attributable to malaria in endemic areas since a significant proportion of asymptomatic children have malaria parasitaemia.”

Kenya has been experiencing some intense malaria intervention over recent years.  This provides a setting where researchers have gotten a handle on the potential reduction in the burden of long term CNS disease because of malaria control activities. Among the findings Kariuki et al. report are that, “From 2002 to 2008, the incidence of all acute symptomatic seizures decreased by … 69.2% with 93.1% of this decrease in malaria-associated seizures.”

Malaria itself imposes major immediate costs on a community from direct service payments and indirect loss of work and of course from loss of life. We should not forget the lingering costs of severe malaria may degrade the educational and occupational capacity and opportunities of community members, leaving such endemic communities mired in poverty. Clearly malaria elimination is an essential contribution to national development.