A randomised controlled trial to compare the efficacy, safety, and tolerability of low dose, short course primaquine in adults with uncomplicated P. vivax malaria in two hospitals in India.

BACKGROUND: Plasmodium vivax remains a major challenge for malaria control and elimination due to its ability to cause relapsing illness. To prevent relapses the Indian National Center for Vector Borne Diseases Control (NCVBDC) recommends treatment with primaquine at a dose of 0.25 mg/kg/day provided over 14 days. Shorter treatment courses may improve adherence and treatment effectiveness. METHODS: This is a hospital-based, randomised, controlled, open-label trial in two centres in India. Patients above the age of 16 years, with uncomplicated vivax malaria, G6PD activity of ≥ 30% of the adjusted male median (AMM) and haemoglobin levels ≥ 8 g/dL will be recruited into the study and randomised in a 1:1 ratio to receive standard schizonticidal treatment plus 7-day primaquine at 0.50 mg/kg/day or standard care with schizonticidal treatment plus 14-day primaquine at 0.25 mg/kg/day. Patients will be followed up for 6 months. The primary endpoint is the incidence risk of any P. vivax parasitaemia at 6 months. Safety outcomes include the incidence risk of severe anaemia (haemoglobin < 8 g/dL), the risk of blood transfusion, a > 25% fall in haemoglobin and an acute drop in haemoglobin of > 5 g/dL during primaquine treatment. DISCUSSION: This study will evaluate the efficacy and safety of a 7-day primaquine regimen compared to the standard 14-day regimen in India. Results from this trial are likely to directly inform national treatment guidelines. TRIAL REGISTRATION: Trial is registered on CTRI portal, Registration No: CTRI/2022/12/048283.

Role of Human Twin Studies to Identify Genetic Linkage of Malaria Pathogenesis and Outcomes.

Malaria remains a major public health challenge that needs attention, especially when the world is aiming at malaria elimination in the near future. It is crucial to understand the underlying genetic factors and epigenetics involved in malaria susceptibility and the dynamics of host immune responses that affect disease outcomes and relapses in Plasmodium vivax and Plasmodium ovale. Studies in newborn and adult twins can help in understanding the comparative roles of environmental and genetic factors on disease pathogenesis and outcome. These studies can help in providing insights into the factors responsible for malaria susceptibility, clinical presentation, responsiveness toward existing as well as candidate antimalarials, and even identification of novel therapeutic targets. The results and outcomes from twin studies can be further applied to the entire population. In the present manuscript, we analyze the available literature on malaria and human twins and discuss the significance and benefits of twin studies to help in better understanding malaria.

Vaccination coverage and breakthrough infections of COVID-19 during the second wave among staff of selected medical institutions in India.

India experienced the second wave of SARS-CoV-2 infection from April 3 to June 10, 2021. During the second wave, Delta variant B.1617.2 emerged as the predominant strain, spiking cases from 12.5 million to 29.3 million (cumulative) by the end of the surge in India. Vaccines against COVID-19 are a potent tool to control and end the pandemic in addition to other control measures. India rolled out its vaccination programme on January 16, 2021, initially with two vaccines that were given emergency authorization-Covaxin (BBV152) and Covishield (ChAdOx1 nCoV- 19). Vaccination was initially started for the elderly (60+) and front-line workers and then gradually opened to different age groups. The second wave hit when vaccination was picking up pace in India. There were instances of vaccinated people (fully and partially) getting infected, and reinfections were also reported. We undertook a survey of staff (front line health care workers and supporting) of 15 medical colleges and research institutes across India to assess the vaccination coverage, incidence of breakthrough infections, and reinfections among them from June 2 to July 10, 2021. A total of 1876 staff participated, and 1484 forms were selected for analysis after removing duplicates and erroneous entries (n = 392). We found that among the respondents at the time of response, 17.6% were unvaccinated, 19.8% were partially vaccinated (received the first dose), and 62.5% were fully vaccinated (received both doses). Incidence of breakthrough infections was 8.7% among the 801 individuals (70/801) tested at least 14 days after the 2nd dose of vaccine. Eight participants reported reinfection in the overall infected group and reinfection incidence rate was 5.1%. Out of (N = 349) infected individuals 243 (69.6%) were unvaccinated and 106 (30.3%) were vaccinated. Our findings reveal the protective effect of vaccination and its role as an essential tool in the struggle against this pandemic.

Ivermectin as an endectocide may boost control of malaria vectors in India and contribute to elimination.

Malaria constitutes one of the largest public health burdens faced by humanity. Malaria control has to be an efficient balance between diagnosis, treatment and vector control strategies. The World Health Organization currently recommends indoor residual spraying and impregnated bed nets as two malaria vector control methods that have shown robust and persistent results against endophilic and anthropophilic mosquito species. The Indian government launched the National Framework for Malaria Elimination in 2016 with the aim to achieve the elimination of malaria in a phased and strategic manner and to sustain a nation-wide malaria-free status by 2030. India is currently in a crucial phase of malaria elimination and novel vector control strategies maybe helpful in dealing with various challenges, such as vector behavioural adaptations and increasing insecticide resistance among the Anopheles populations of India. Ivermectin can be one such new tool as it is the first endectocide to be approved in both animals and humans. Trials of ivermectin have been conducted in endemic areas of Africa with promising results. In this review, we assess available data on ivermectin as an endectocide and propose that this endectocide should be explored as a vector control tool for malaria in India.

Mefloquine as a prophylaxis for malaria needs to be revisited.

According to WHO, 2019 witnessed 229 million cases of malaria globally, of which Africa accounted for 94% of cases. Early diagnosis and treatment are the basis of malaria management, and the need for good chemoprophylaxis especially for people travelling to endemic areas is vital. There are a number of drug options available for the prophylaxis of malaria, mefloquine being one of the drugs used. Mefloquine has been around from the 1970s, and was developed in the United States keeping in mind the soldiers that were being deployed to areas where chloroquine resistant strains of Plasmodium were discovered. Mefloquine was preferred for its once a week dosage. Within a decade of its introduction, reports of the side effects associated with its long-term use surfaced. Mefloquine is now reported to cause a myriad of neuropsychiatric side effects including anxiety, sleep disturbance, depression, dizziness and frank psychosis, especially in patients with pre-existing psychiatric disorders. Many countries like the United States and the United Kingdom have updated their drug boxes to include the warning of these potential neuropsychiatric effects. This paper reviews the side effects of mefloquine and why there is a need to revisit its use in Indian drug policy.

Coverage enhancement and community empowerment via commercial availability of the long-lasting nets for malaria in India.

Achieving malaria elimination goal in India will require supplemental measures to plug in the gaps in implementation of malaria control programmes. Use of long-lasting insecticide nets is one of the two core interventions for vector control in malaria. The most common distribution channel is free delivery via national malaria control programme of various countries and in India, this is the only channel to provide nets to the masses. Understandably, there are gaps in the optimum coverage of at-risk population due to multiple reasons ranging from population growth to time lag in replacements, emergency conditions like floods and logistical impediments among others. At this juncture, it is crucial for India to explore complementary routes to expand access for nets by its people and one is making them available in private sector at an affordable price. The commercial availability of nets offers several advantages like filling in coverage gaps, overcoming additional requirements by families and financial resources being freed up for poor households. However, there are barriers to the successful operationalization of net commercialization like affordability issues, economic viability for manufacturers, regulatory issues etc. All the so-called barriers can be addressed in a concerted and pragmatic way to make access and availability of nets in private market a reality as that is a need of the hour, if India wants to achieve malaria elimination goal by 2030.