The global procurement landscape of leishmaniasis medicines.

Ensuring access to essential medicines for leishmaniasis control is challenging, as leishmaniasis is a very small and unattractive market for pharmaceutical industry. Furthermore, control programmes are severely underfunded. We conducted an analysis of global procurement of leishmaniasis medicines for the past 5 years in order to shed light on the current leishmaniasis market landscape and supply and demand dynamics. We estimated global demand of each leishmaniasis medicines, the amount of each medicine required to treat all reported cases, based on the number of cases reported to WHO and the first-line treatment regimen used in each country. Procurement data were obtained from procurement agencies, international organizations, WHO, national leishmaniasis programmes and manufacturers. Expert interviews were conducted to have a better understanding of how medicines were procured and used. The comparison of estimated need and procurement data indicated discrepancies in supply and demand at global level as well as in the most endemic countries. The extent of the gap in supply was up to 80% of the needs for one of the leishmaniasis medicines. Mismatch between supply and demand was much wider for cutaneous leishmaniasis than visceral leishmaniasis. This study presents a current picture of procurement patterns and imbalance in global supply and demand. Addressing improved access and supply barriers requires concerted and coordinated efforts at the global and national levels. Priority actions include setting up a procurement coordination mechanism among major procurers, partners and national programmes where forecasting and supply planning is jointly developed and communicated with manufacturers. In addition, continuous engagement of manufacturers and advocacy is critical to diversify the supplier base and ensure quality-assured and affordable generic medicines for leishmaniasis.

Exploring global and country-level barriers to an effective supply of leishmaniasis medicines and diagnostics in eastern Africa: a qualitative study.

OBJECTIVES: To understand stakeholders' perceptions of the access barriers to quality-assured diagnostics and medicines for leishmaniasis in the high-burden region of eastern Africa, and to identify key bottlenecks to improve the supply of commodities for neglected tropical diseases. DESIGN: Desk reviews and qualitative in-depth interview study with purposive sampling. METHODS: A landscape analysis through literature and desk review was performed. Next, 29 representatives from international organisations, non-governmental agencies, national control programmes from six countries (Ethiopia, Kenya, Somalia, South Sudan, Sudan and Uganda) and manufacturers were interviewed between May and July 2018. Participants were selected purposively and expanded through a snowballing technique.Data analysis was aided by NVivo, applying the framework method as a part of the thematic content analysis approach. RESULTS: The barriers along the visceral leishmaniasis (VL) supply chain were identified as emerging themes, grouped across supply chain activities and health systems component(s). Stakeholders expressed the perception of progress, but bottlenecks persist. VL medicines, in general, lack multisource production capacity and with small market volume, expansion of suppliers is difficult. Procurement is plagued by forecasting difficulties, complex regulatory policies and procedures, and distribution challenges. Weak communication and coordination across different levels resulted in shortages and loss of trust among different actors. Cross-cutting issues spanned from limited political and resource commitment due to low awareness and limited in-country capacity. However, study respondents were optimistic to pursue several remedies, most importantly to build bridges between supply and demand sides through continued dialogue and collaborations. Diagnostics supply has mostly been overlooked; thus, improved investment in this area is needed. CONCLUSIONS: Addressing supply barriers in eastern Africa requires consistent, specific efforts at the global and national levels, progressing from current partnerships and agreements. Priority actions include pooled procurement, improved forecast, and increased commitment and resources. Sustainability remains an elusive goal, yet to be integrated into discussions moving forward.

Future Priorities in Tackling Infections Due to Brain-Eating Amoebae.

Brain-eating amoebae (Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri) can cause opportunistic infections involving the central nervous system. It is troubling that the mortality rate is more than 90% despite advances in antimicrobial chemotherapy over the last few decades. Here, we describe urgent key priorities for improving outcomes from infections due to brain-eating amoebae.

New world cutaneous leishmaniasis: obstacles in initiating treatment with sodium stibogluconate in 2 travelers from Texas.

New World cutaneous leishmaniasis (CL) is considered in the differential diagnosis for patients with nonhealing ulcers and a history of travel to high-risk areas. For patients at risk for progression to mucocutaneous leishmaniasis, first-line treatment in the United States entails the use of sodium stibogluconate (SSG), which is obtained from the Centers for Disease Control and Prevention (CDC) under an investigational drug protocol. We report 2 cases of New World CL in travelers to endemic areas who were diagnosed and treated with SSG. These cases demonstrate the logistics of coordinating with the CDC to definitively diagnose New World CL and initiate the necessary treatment.

Cutaneous leishmaniasis in the Jordanian side of the Jordan Valley: severe under-reporting and consequences on public health management.

OBJECTIVE: To test if cutaneous leishmaniasis (CL) is under-reported in the Jordanian Mid Jordan Valley, with resultant serious consequences for drug supply. METHODS: For 2001-2003, prescribed amounts of drug and laboratory log-books were investigated to estimate CL cases reported in Jordanian Mid Jordan Valley. From April 2004 to May 2005, passive detection and focused active 'index case cluster'-directed detection were used. RESULTS: An average of 75/100,000 cases per year was estimated to have occurred 2001-2003, resulting in under-reporting by a factor of 47. In 2004/2005, 313/100,000 cases per year were passively detected. Active case-finding detected additional cases. CONCLUSION: Cutaneous leishmaniasis is severely under-reported in Jordanian Mid Jordan Valley, which impacts its eradication.

TDR collaboration with the pharmaceutical industry.

TDR's research programme was initiated in 1976 at the same time that the pharmaceutical industry began to withdraw from the discovery and development of new drugs for tropical diseases. TDR collaborated with the industry right from the start, its prime objective initially being to ensure that candidate drugs already in the development pipeline, such as praziquantel, mefloquine, ivermectin, halofantrine and atovaquone/proguanil, were not shelved. It became clear during the 1980s that once candidate drugs in these existing pipelines had been processed, that would be it. TDR therefore developed a number of other ways for collaboration, including testing compounds already in development in companies for other therapeutic areas. One candidate identified in this way was an oral formulation of miltefosine, in development in Asta Medica for an antitumour indication. A joint Asta Medica (later Zentaris)/TDR development project was agreed, and despite its fair share of traumas during the development process, miltefosine is now registered for the treatment of visceral leishmaniasis in India, Germany and Colombia. This example of a successful TDR/pharmaceutical industry collaboration lives on in the various Public Private Partnerships such as the new Medicines for Malaria Venture that TDR helped to spawn.

Progress in the treatment of a neglected infectious disease: visceral leishmaniasis.

Visceral leishmaniasis (kala-azar) is a disseminated intracellular protozoal infection. Most cases (90%) occur in the rural regions of five countries: India, Sudan, Nepal, Bangladesh and Brazil. As with other infectious diseases embedded in high-level poverty, developing and/or delivering new treatments for visceral leishmaniasis had been painfully slow or nonexistent. However, despite persistent unresolved obstacles (e.g., drug affordability), renewed interest in visceral leishmaniasis and numerous successful treatment trials have combined to turn a therapeutic corner in the past 5 years, yielding new alternatives to conventional pentavalent antimony. Advances include the use of low-cost generic pentavalent antimony, rediscovery of amphotericin B, short-course regimens via lipid formulations of amphotericin B, retesting injectible paromyomycin and, of clear-cut importance, identifying miltefosine (Impavido, Zentaris) as the first effective oral therapy for this neglected disease.

Visceral leishmaniasis: consequences of a neglected disease in a Bangladeshi community.

Visceral leishmaniasis, or kala azar (KA), affects the rural poor, causing significant morbidity and mortality. We examined the epidemiologic, social, and economic impact of KA in a village in Bangladesh. A population-based survey among 2,348 people demonstrated a KA incidence of 2% per year from 2000 to 2002, with a case-fatality rate of 19% among adult women, compared with 6-8% among other demographic groups. Kala azar cases were geographically clustered in certain sections of the village. Anti-leishmanial drug shortages and the high cost of diagnosis and treatment caused substantial emotional and economic hardship for affected families. Communities wanted to learn more about KA, and were willing to take collective action to confront the problems it causes. To decrease the KA burden in endemic areas, community efforts should be supplemented with effective treatment programs to ensure access to appropriate and affordable diagnosis and case management.

NTZ: advisory committee votes against approval.

AIDS: The Food and Drug Administration's (FDA) Antiviral Drugs Advisory Committee did not approve NTZ as a treatment for cryptosporidiosis. ACTG 336, a government-sponsored study expected to provide data supporting NTZ, closed due to poor enrollment. Without this trial, UNIMED submitted data that the FDA found incomplete. NTZ is reported to have a wide scope of antiparasitic activity without the side effects presented by other similar drugs. NTZ may also be effective for microsporidiosis, giardia, and other parasites. Advocates are concerned that rejection of NTZ leaves limited treatment options for those afflicted with cryptosporidiosis and are suggesting new study designs.^ieng

NTZ for cryptosporidiosis.

AIDS: The Food and Drug Administration (FDA) has given permission for increasing the size of the nitazoxanide (NTZ) expanded access program designed for studying the treatment of cryptosporidiosis. There are apparently no serious side effects. There is now no limit to the number of people with HIV-related cryptosporidiosis who can access the drug through the open label program. Participants will be randomized to receive either 1,000 or 2,000 mg per day of NTZ for 1 month. It is noted that the PWA Health Group in New York still offers NTZ to anyone with a prescription who does not qualify for the expanded access program or who does not want to participate in the phase II/III study.^ieng

Cryptosporidiosis: NTZ available at buyers' club; customs holds 2nd shipment.

AIDS: NTZ (nitazoxanide), recently approved in Mexico, is available from the PWA Health Group in New York as an experimental treatment against cryptosporidiosis. NTZ is being studied as a treatment for many parasites in developing countries. In the U.S., NTZ is in phase I trials for cryptosporidiosis, which causes severe diarrhea in persons with AIDS. A compassionate access program recently was expanded from 100 to 150 slots, but many people were still not able to obtain the drug. In addition, on June 21, 1996, a U.S. Customs office seized half of the PWA Health Group shipment of NTZ. The PWA Health Group is confident the shipment will be released soon.^ieng