Malaria continues to be a major public health problem in Pakistan. According to the World Malaria Report 2021, 63.88 million (28.9%) people in Pakistan live in areas with a high risk of malaria transmission. Plasmodium vivax is the prominent malaria parasite in Pakistan, accounting for nearly 80% of its total cases [1]. Pakistan’s vivax burden is also one of the highest in the Asia Pacific region with more than 290,000 reported cases in 2020 [1]. Estimates vary widely as to the proportion of severe vivax cases represented in hospital admissions for malaria. Some sources have put the figure as low as 0.8% of admissions [2], whereas others have estimated them to be as high as 31.2% among children [3], and 37.5% among adults [4].

Vivax malaria poses a huge threat to elimination. It is harder to cure than other forms of malaria, requiring treatment of both the blood-stage and liver-stage of the disease – something known as radical cure. If a liver-stage or relapse prevention treatment is not given, a form of the vivax parasite can lie dormant in a person’s liver and then reactivate causing the person to fall ill with a new episode of malaria. This is not only a significant risk for the patient’s health, but it also represents a renewed risk of transmission. This underlines the need for additional reliable, well tolerated, and effective radical cure for P. vivax.

Case management of uncomplicated P. vivax, as specified in the National Strategic Plan for Malaria Elimination 2021-2035, includes the radical cure treatment with a combination of Chloroquine (CQ) for 3 days and Primaquine (PQ) for 14 days to ensure elimination of parasites in the liver. The strategic plan further proposes gradual rollout of screening for G6PD deficiency prior to PQ administration[1], and introduction of directly observed/supervised treatment of P. vivax cases, particularly in the elimination phase.

Since 2021, the APMEN Vivax Working Group (VxWG) has been hosted by Medicines for Malaria Venture (MMV), who also co-leads the Partnership for Vivax Elimination (PAVE) initiative that supports endemic countries in achieving their P. vivax malaria elimination goals.

At the start of the year, during a 2-day workshop, APMEN VxWG with support from the Secretariat conducted a Readiness Planning for Vivax Elimination workshop in Islamabad, Pakistan - to develop a vivax elimination road map and timeline based on identified gaps and risks. In addition to representatives from the Directorate of Malaria Control (DoMC), several provincial level malaria stakeholders from Gilgit-Baltistan, Baluchistan, Sindh, Merged Tribal Areas, Azad Jammu Kashmir and Punjab, took part in this workshop.

The key outcomes of the workshop were:

• A detailed description of key priorities and gaps developed by the Directorate of Malaria Control Program, Provincial Malaria Programs and other stakeholders for eliminating vivax malaria in Pakistan
• A list of tools and strategies that could be considered to achieve vivax elimination
• An understanding of what is required to implement new tools or strategies to accelerate access to radical cure for vivax malaria

After the workshop, outlines of the existing policy-making process for malaria and procurement processes for antimalarials relevant to the adoption of new tools and strategies were also mapped.

At the workshop, and through subsequent discussions, several challenges with respect to vivax malaria elimination were highlighted. The main challenges included, confirmatory diagnosis of all malaria and reporting, availability of PQ in a large proportion of public, and all private sector facilities, health worker compliance with treatment protocols linked to fear of haemolysis in G6PD deficient patients[2], patient adherence to 14 day PQ regime, The APMEN VxWG shared information on the various new tools and options for radical cure of P. vivax malaria that the WHO GMP are considering, the advantages of different options, health system  requirements, and challenges to implementing new tools.

“We are at an exciting stage for vivax malaria elimination – where new tools are becoming available that could enable National Programs to achieve their goals. However, integrating new tools requires support from within the health system - from efficient policy processes to strong pharmacovigilance. In addition to innovative new tools, both the APMEN VxWG and PAVE seek to identify innovative processes to ensure that the road ahead for the inclusion of new tools into policies and practice is smooth” - Dr Caroline Lynch, Co-Chair of APMEN VxWG and Regional Advisor for MMV

The participants conducted a priority ranking exercise for key questions that would aid the program in developing and implementing a strategy for vivax elimination. The priority questions agreed upon by the group focused on technical support, funding for implementation, training of health workers, feasibility of private sector accessing new tools and interventions for increasing patient adherence. Participants validated the results of the priority ranking exercise and added the importance of health economic analysis for adoption of new radical cure tools as another high priority.

The participants also identified challenges, listed readiness activities, risks and mitigation measures for vivax radical cure implementation, under the four thematic areas- malaria case management, surveillance, program management, logistics and supply chain management. The discussion covered the need for elimination, programmatic readiness for elimination, the inability of the program to pursue elimination as envisioned in the national and provincial strategic plans, unavailability of resources to scale up the malaria control and elimination activities in non-Global Fund supported districts, and the need for programmatic shift to ensure universal coverage of malaria control and elimination among others.

After the discussions, the group concluded that tafenoquine (TQ)- a new single dose treatment, could be a suitable treatment option for vivax malaria to address the patient adherence issues related to PQ. However, as TQ is just one additional tool in the vivax radical cure toolkit, discussions continued as to how to ensure the availability of PQ for all at risk patients. The program planned to follow up with the Drug Regulatory Authority of Pakistan on the registration of TQ and explore expanding access to PQ. In addition, the group also decided to explore the possibility of incorporating studies on G6PD deficiency prevalence and patients’ adherence to the 14-day PQ treatment regime in the planned Malaria Indicator Survey in 2022.

The workshop was complemented by a field visit to Punjab- a near elimination province, which aims to report zero incidences of malaria by 2025. During the visit, Dr. Muhammad Mukhtar, the Director of DoMC, consulted with the health department of Punjab to discuss the elimination roadmap in their context and obtain their approval.

There is an acute need for timely introduction and scale up of new treatment regimens for vivax malaria to achieve malaria elimination targets. This workshop was very useful for the national and provincial malaria programs in understanding the priorities and mapping the activities and policy process that would need to be in place to implement a vivax specific elimination strategy.”- Dr. Muhammad Mukhtar, Director, Directorate of Malaria Control, Ministry of National Health Services, Government of Pakistan

References

1. World Health Organization. World Malaria Report 2021.
2. Akhlaq A, Ghanchi N, Usmani B, Shahzad R, Rahim A, Wasay M, et al. Neurological complications in patients with Plasmodium vivax malaria from Karachi, Pakistan. J R Coll Physicians Edinb. 2018;48(3):198–201.
3. Shaikh S, Memon H, Iohano B, Shaikh A, Ahmed I, Baird JK. Severe disease in children hospitalized with a diagnosis of Plasmodium vivax in south-eastern Pakistan. Malaria Journal. 2012 May 2;11(1):144.
4. Zubairi ABS, Nizami S, Raza A, Mehraj V, Rasheed AF, Ghanchi NK, et al. Severe Plasmodium vivax Malaria in Pakistan. Emerg Infect Dis. 2013 Nov;19(11):1851–4.