Maruyama et al. Non-Leishmania Parasite in Fatal Visceral Leishmaniasis–like Disease, Brazil. Emerging Infectious Diseases DOI: 10.3201/eid2511.181548 (2019).

“…..During 2011–2012, we characterized 2 parasite strains, LVH60 and LVH60a, isolated from an HIV-negative man when he was 64 years old and 65 years old (Table; Appendix). Treatment-refractory VL-like disease developed in the man; signs and symptoms consisted of weight loss, fever, anemia, low leukocyte and platelet counts, and severe liver and spleen enlargements. VL was confirmed by light microscopic examination of amastigotes in bone marrow aspirates and promastigotes in culture upon parasite isolation and by a positive rK39 serologic test results. Three courses of liposomal amphotericin B resulted in no response. At the third hospital admission, the illness resembled diffuse cutaneous leishmaniasis, in which several disseminated papular skin lesions were observed (Appendix Figure 1, panel A), and a skin biopsy revealed macrophages filled with amastigotes (Appendix Figure 1, panel B), which his liver biopsy results also showed (Appendix Figure 1, panel C). During this third admission, the LVH60a strain was isolated from the skin. Dermal lesions known as post–kala-azar dermal leishmaniasis (PKDL) have rarely been reported in Brazil (13), and the clinical aspect of the disseminated papular skin lesions on this patient differed from the clinical presentation of PKDL. Because his illness did not respond to therapy, the patient underwent splenectomy. He died of disease and surgical complications...…”

NIH

A new study published this week online in Emerging Infectious Diseases suggests that transmission of a protozoan parasite from insects may also cause leishmaniasis-like symptoms in people. The parasite, however, does not respond to treatment with standard leishmaniasis drugs. The research was conducted by scientists at the Federal Universities of Sergipe and São Carlos, the University of São Paulo, and the Oswaldo Cruz Foundation, all in Brazil, along with investigators at the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health.

Leishmaniasis is a parasitic disease found in parts of the tropics, subtropics, and southern Europe. It is classified as a neglected tropical disease and is often transmitted by the bite of some sand flies. The most common forms of leishmaniasis are cutaneous, which causes skin sores, and visceral, which affects several internal organs (usually spleen, liver, and bone marrow). According to the World Health Organization, each year between 50,000 and 90,000 people become sick with visceral leishmaniasis (kala-azar), a form of the disease that attacks the internal organs and is fatal in more than 95 percent of cases left untreated. During the last several decades, researchers have described rare cases of patients co-infected with both Leishmania and other groups of protozoan parasites that usually infect insects, including Crithidia. The current study of parasites isolated from a Brazilian patient confirms that Crithidia parasites also can infect people.

Galway/CDC

The 63-year-old patient initially sought treatment for the symptoms of visceral leishmaniasis, including weight loss, fever, anemia, and an enlarged liver and spleen. However, after eight months of standard leishmaniasis treatment, the patient’s symptoms had not improved. The patient developed widespread skin lesions with poorly defined edges (unlike the small lesions with well-defined edges that sometimes appear after treatment for visceral leishmaniasis) and ultimately died.

To determine the cause of disease, researchers cultured parasites taken from the patient’s bone marrow and skin lesions, sequenced their genomes, and discovered that the parasites were not closely related to known disease-causing Leishmania parasites. Instead, they were more closely related to Crithidia fasciculata, a parasite that usually colonizes mosquitoes. To confirm that these Crithidia parasites could infect mammals, the researchers exposed mice to the parasites isolated from the patient, both intravenously and by injection into the skin, and found that both types of parasite infected the liver. The parasites collected from the patient’s skin also caused skin lesions in the mice.

The study raises concerns that the Brazilian patient might not be an isolated case. If Crithidia infections represent an emerging infectious disease in people, there will be an urgent need to develop novel effective treatments, the researchers write. They expressed concern that the disease may be mosquito-borne because Anopheles and Culex mosquitoes can host the Crithidia parasite. More research will be needed to find other human cases, confirm the parasite’s range and host species, and discover potential treatments, the authors note.

Article

Maruyama et al. Non-Leishmania Parasite in Fatal Visceral Leishmaniasis–like Disease, Brazil. Emerging Infectious Diseases DOI: 10.3201/eid2511.181548 (2019).

CDC

EurekaAlert

“……..Global warming has allowed mosquitoes, ticks and other disease-carrying insects to proliferate, adapt to different seasons, and invade new territories across Europe over the past decade–with accompanying outbreaks of dengue in France and Croatia, malaria in Greece, West Nile Fever in Southeast Europe, and chikungunya virus in Italy and France. …….”

DNDI

“….There are different forms of leishmaniasis, a parasitic disease transmitted by the bite of a sand fly, barely visible to the human eye: visceral leishmaniasis (kala-azar), cutaneous leishmaniasis, and mucocutaneous leishmaniasis. Post-kala-azar dermal leishmaniasis is usually a sequel of visceral leishmaniasis that appears as macular, papular or nodular rash usually on the face, upper arms, and other parts of the body…..”

Libya Observer

“….[He] explained that there is no cure at the current time for the disease in Libya, noting that the cost of treatment for this disease is prohibitively expensive and could amount to 10 thousand Libyan dinars per person….. Zliten Municipality warned against the spread of leishmaniasis, declaring that 351 cases were recorded in the city in 2017…..Leishmaniasis is a parasitic disease spread to humans by bites of sandflies that are usually active from May to September each year…..”

 Credit: C. Bern, CDC

 (Credit: B. Arana, MERTU, Guatemala)

Daily Iowan

“….Leishmaniasis is a tropical infectious disease found in 98 countries around the globe. According to an estimate from the World Health Organization, it kills approximately 20,000 to 40,000 people a year in mostly five countries: Bangladesh, Brazil, Ethiopia, India, and Sudan. It also kills thousands of dogs.….”

CDC

Our Formulary

WHO

The call came from the WHO Director-General in May 2016 for a renewed attack on the global spread of vector-borne diseases.

“What we are seeing now looks more and more like a dramatic resurgence of the threat from emerging and re-emerging infectious diseases,” Dr Margaret Chan told Member States at the Sixty-ninth World Health Assembly. “The world is not prepared to cope.”

Dr Chan noted that the spread of Zika virus disease, the resurgence of dengue, and the emerging threat from chikungunya were the result of weak mosquito control policies from the 1970s. It was during that decade that funding and efforts for vector control were greatly reduced.

‘Vector control has not been a priority’

Dr Ana Carolina Silva Santelli has witnessed this first-hand. As former head of the programme for malaria, dengue, Zika and chikungunya with Brazil’s Ministry of Health, she saw vector-control efforts wane over her 13 years there. Equipment such as spraying machines, supplies such as insecticides and personnel such as entomologists were not replaced as needed. “Vector control has not been a priority,” she said.

Today more than 80% of the world’s population is at risk of vector-borne disease, with half at risk of two or more diseases. Mosquitoes can transmit, among other diseases, malaria, lymphatic filariasis, Japanese encephalitis and West Nile; flies can transmit onchocerciasis, leishmaniasis and human African trypanosomiasis (sleeping sickness); and bugs or ticks can transmit Chagas disease, Lyme disease and encephalitis.

Together, the major vector-borne diseases kill more than 700 000 people each year, with populations in poverty-stricken tropical and subtropical areas at highest risk. Other vector-borne diseases, such as tick-borne encephalitis, are of increasing concern in temperate regions.

Rapid unplanned urbanization, massive increases in international travel and trade, altered agricultural practices and other environmental changes are fuelling the spread of vectors worldwide, putting more and more people at risk. Malnourished people and those with weakened immunity are especially susceptible.

A new approach

Over the past year, WHO has spearheaded a new strategic approach to reprioritize vector control. The Global Malaria Programme and the Department of Control of Neglected Tropical Diseases – along with the Special Programme for Research and Training in Tropical Diseases, have led a broad consultation tapping into the experience of ministries of health and technical experts. The process was steered by a group of eminent scientists and public health experts led by Dr Santelli and Professor Thomas Scott from the Department of Entomology and Nematology at the University of California, Davis and resulted in the Global Vector Control Response (GVCR) 2017–2030.

• Global Vector Control Response (GVCR) 2017–2030

At its Seventieth session, the World Health Assembly unanimously welcomed the proposed response.

The GVCR outlines key areas of activity that will radically change the control of vector-borne diseases:

• Aligning action across sectors, since vector control is more than just spraying insecticides or delivering nets. That might mean ministries of health working with city planners to eradicate breeding sites used by mosquitoes;
• Engaging and mobilizing communities to protect themselves and build resilience against future disease outbreaks;
• Enhancing surveillance to trigger early responses to increases in disease or vector populations, and to identify when and why interventions are not working as expected; and
• Scaling-up vector-control tools and using them in combination to maximize impact on disease while minimizing impact on the environment.

Specifically, the new integrated approach calls for national programmes to be realigned so that public health workers can focus on the complete spectrum of relevant vectors and thereby control all of the diseases they cause.

Recognizing that efforts must be adapted to local needs and sustained, the success of the response will depend on the ability of countries to strengthen their vector-control programmes with financial resources and staff.

A call to pursue novel interventions aggressively

The GVCR also calls for the aggressive pursuit of promising novel interventions such as devising new insecticides; creating spatial repellents and odour-baited traps; improving house screening; pursuing development of a common bacterium that stops viruses from replicating inside mosquitoes; and modifying the genes of male mosquitoes so that their offspring die early.

Economic development also brings solutions. “If people lived in houses that had solid floors and windows with screens or air conditioning, they wouldn’t need a bednet,” said Professor Scott. “So, by improving people’s standard of living, we would significantly reduce these diseases.”

The call for a more coherent and holistic approach to vector control does not diminish the considerable advances made against individual vector-borne diseases.

Malaria is a prime example. Over the past 15 years, its incidence in sub-Saharan Africa has been cut by 45% – primarily due to the massive use of insecticide-treated bed nets and spraying of residual insecticides inside houses.

But that success has had a down side.

“We’ve been so successful, in some ways, with our control that we reduced the number of public health entomologists – the people who can do this stuff well,” said Professor Steve Lindsay, a public health entomologist at Durham University in Britain. “We’re a disappearing breed.”

The GVCR calls for countries to invest in a vector-control workforce trained in public health entomology and empowered in health care responses.

“We now need more nuanced control – not one-size-fits-all, but to tailor control to local conditions,” Professor Lindsay said. This is needed to tackle new and emerging diseases, but also to push towards elimination of others such as malaria, he said.

Dr Lindsay noted that, under the new strategic approach, individual diseases such as Zika, dengue and chikungunya will no longer be considered as separate threats. “What this represents is not three different diseases, but one mosquito – Aedes aegypti,” said Professor Lindsay.

GVCR dovetails with Sustainable Development Goals

The GVCR will also help countries achieve at least 6 of the 17 Sustainable Development Goals. Of direct relevance are goal 3 on good health and well-being, goal 6 on clean water and sanitation, and goal 11 on sustainable cities and communities.

The GVCR goals are ambitious – to reduce mortality from vector-borne diseases by at least 75% and incidence by at least 60% by 2030 – and to prevent epidemics in all countries.

The annual price tag is US$ 330 million globally, or about 5 cents per person – for workforce, coordination and surveillance costs. This is a modest additional investment in relation to insecticide-treated nets, indoor sprays and community-based activities, which usually exceed US$ 1 per person protected per year.

It also represents less than 10% of what is currently spent each year on strategies to control vectors that spread malaria, dengue and Chagas disease alone. Ultimately, the shift in focus to integrated and locally adapted vector control will save money.

‘A call for action’

Dr Santelli expressed optimism that the GVCR will help ministries of health around the world gain support from their governments for a renewed focus on vector control.

“Most of all, this document is a call for action,” said Dr Santelli, who now serves as deputy director for epidemiology in the Brasilia office of the U.S. Centers for Disease Control and Prevention.

It will not be easy, she predicts. The work to integrate vector-control efforts across different diseases will require more equipment, more people and more money as well as a change in mentality. “The risk of inaction is greater,” said Dr Santelli, “given the growing number of emerging disease threats.” The potential impact of the GVCR is immense: to put in place new strategies that will reduce overall burden and, in some places, even eliminate these diseases once and for all.

CORDS

“…New research out today (9 Feb 2016); the Leishmaniasis Gap Analysis Report and Action Plan carried out in Albania, Jordan and Pakistan during 2015, shows despite its worldwide prevalence and disastrous impact on the lives of millions, leishmaniasis is still very much a growing, neglected disease, mainly affecting impoverished communities, living in poor conditions, without adequate access to shelter, healthcare and medication…..”

“….Leishmaniasis, one of the world’s oldest recorded diseases dating back to the 7^th century BC, is an entirely treatable parasitic disease spread by female sandflies. Around 310,000,000 people are estimated to be at risk globally, with around 1.6 million new cases each year across 98 countries. The cutaneous form of the disease can lead to distressing and disfiguring skin ulcers and scarring, while visceral leishmaniasis, which affects organs such as the liver and spleen, is invariably fatal if not treated. Over 40,000 people die from the disease every year, making it the second-largest parasitic killer in the world after malaria.

The purpose of the study is to improve the capacity for the diagnosis, treatment and control of leishmaniasis and other vector borne diseases.

Our research found that;

• leishmaniasis is highly correlated with poverty, malnutrition and other diseases which affect immunity, as well as factors such as crowded living conditions and poor sanitation.

• the real health burden of leishmaniasis remains largely unknown with only 600,000 of the estimated 1.6 million cases each year being diagnosed and treated. This is because those who are most affected are from marginalised communities in rural areas or urban slums, who are unable to seek medical attention because of cost and lack of access to treatment

• in the majority of cases leishmaniasis cannot be transmitted directly from an infected person or animal to another person. Rather it requires the presence of female sandfly vectors to spread the disease. It is not therefore a disease that is likely to spread in areas such as Western Europe, which generally lack sandflies and have healthy populations with good sanitation and access to high-quality healthcare

• leishmaniasis has been ignored largely because of its association with poverty and the limited capacity of governments and aid agencies to deal with its complex epidemiology

• it has also been a low priority for multinational pharmaceutical companies to invest in research to develop effective vaccines and therapies……”