Assessing the Operational Feasibility of Integrating Point-of-Care G6PD Testing into Plasmodium vivax Malaria Management in Vietnam.

Plasmodium vivax cases represent more than 50% of a diminishing malaria case load in Vietnam. Safe and effective radical cure strategies could support malaria elimination by 2030. This study investigated the operational feasibility of introducing point-of-care quantitative glucose-6-phosphate dehydrogenase (G6PD) testing into malaria case management practices. A prospective interventional study was conducted at nine district hospitals and commune health stations in Binh Phuoc and Gia Lai provinces in Vietnam over the period of October 2020 to October 2021. The STANDARD™ G6PD Test (SD Biosensor, Seoul, Republic of Korea) was incorporated to inform P. vivax case management. Case management data and patient and health care provider (HCP) perspectives, as well as detailed cost data were collected. The G6PD test results were interpreted correctly by HCP and the treatment algorithm was adhered to for the majority of patients. One HCP consistently ran the test incorrectly, which was identified during the monitoring and resulted in provision of refresher training and updating of training materials and patient retesting. There was wide acceptability of the intervention among patients and HCP albeit with opportunities to improve the counseling materials. Increasing the number of facilities to which the test was deployed and decreases in the malaria cases resulted in higher per patient cost for incorporating G6PD testing into the system. Commodity costs can be reduced by using the 10-unit kits compared to the 25 unit kits, particularly when the case loads are low. These results demonstrate intervention feasibility while also highlighting specific challenges for a country approaching malaria elimination.

A Surge in Malaria Cases in the Eastern Health Region of Saudi Arabia During the COVID-19 Pandemic.

Background Malaria transmission was stopped on most of the vast area of the Kingdom of Saudi Arabia. However, the pandemic of coronavirus disease (COVID-19) has negatively affected the efforts to control malaria. For instance, COVID-19 was reported to induce a relapse of malaria that is caused by Plasmodium vivax. Furthermore, physicians' attention toward COVID-19 can only result in neglect and delayed diagnosis of complicated malaria cases. These factors, among others, might have contributed to an increase of malaria cases in Dammam, Saudi Arabia. Thus, this study was conducted to examine the effects of COVID-19 on malarial cases. Methods The medical records of all patients who were treated at Dammam Medical Complex for malaria between July 1, 2018, and June 30, 2022, were reviewed. Malaria cases were compared between the pre-COVID-19 period (between July 1, 2018, and June 30, 2020) and the COVID-19 period (between July 1, 2020, and June 30, 2022). Results A total of 92 malaria cases occurred in the total study period. There were 60 cases of malaria in the COVID-19 period as opposed to only 32 cases in the pre-COVID-19 period. All the cases were imported from the endemic Saudi southern areas or from outside the country. Eighty-two patients (89.1%) were males. Most of them were Sundaneses (39 patients, 42.4%), Saudis (21 patients, 22.8%), and tribal peoples (14 patients, 15.2%). Fifty-four patients (58.7%) were infected with Plasmodium falciparum. Seventeen patients (18.5%) were infected with Plasmodium vivax. Another 17 patients (18.5%) had a mixed infection with both Plasmodium falciparum and Plasmodium vivax. A trend toward more infected stateless tribal patients was observed in the COVID-19 period compared to the pre-COVID-19 period (21.7% vs 3.1%). A similar trend was noticed for mixed malarial infections with both Plasmodium falciparum and Plasmodium vivax (29.8% vs 0%) with a P value of less than 0.01. Conclusion Malaria cases were almost doubled during the COVID-19 pandemic as compared to the pre-pandemic era signifying the negative effects of the pandemic on malaria epidemiology. The cases increased for a variety of causes that include alternation of health-seeking behaviors, changes in healthcare structures and regulations, and the interruption of malaria preventive services. Future research is needed to study the long-term effects of the changes imposed by the COVID-19 pandemic and to mitigate the effects of any future pandemic on malaria control. As two patients from our cohort were diagnosed with malaria based on blood smears, although they had negative rapid detection tests (RDTs), we recommend testing all the patients who are suspected to have malaria with both RDTs and peripheral blood smears.

An imported case of ovale malaria in Xinjiang during the epidemic period of COVID-19.

On December 13, 2020, Yutian County People's hospital reported one imported malaria case in Hotan, Xinjiang. The patient had worked and lived in Yaounde, Cameroon, from January to September 2020. He was infected with malaria twice in March and May 2020. Antimalarial treatment was administrated by the team doctor for 2-3 days in each treatment. The treatment was stopped after the symptoms improved. The patient returned to China on September 16 and was hospitalized on December 13 due to a high fever of 39! and upper respiratory symptoms. Multiple detections of COVID-19 nucleic acid showed negative results. Peripheral blood from the patient was taken for Plasmodium rapid diagnostic test (RDT), which showed a positive result suggesting non Plasmodium falciparum infection. Ring stage P. ovale was found in the blood smear. Nested PCR showed positive for P. ovale. A diagnosis of imported ovale malaria was made. The patient was administrated with 4 dihydroartemisinin piperaquine tablets and 3 primaquine phosphate tablets daily. The malaria parasite test became negative after 8 days of treatment. The patient was followed up for 3 months after discharge and had no symptoms of chills or fever.Copyright © 2022, National Institute of Parasitic Diseases. All rights reserved.

Glucose-6-Phosphate Dehydrogenase (G6PD) Measurement Using Biosensors by Community-Based Village Malaria Workers and Hospital Laboratory Staff in Cambodia: A Quantitative Study.

Vivax malaria can relapse after an initial infection due to dormant liver stages of the parasite. Radical cure can prevent relapses but requires the measurement of glucose-6-phosphate dehydrogenase enzyme (G6PD) activity to identify G6PD-deficient patients at risk of drug-induced haemolysis. In the absence of reliable G6PD testing, vivax patients are denied radical curative treatment in many places, including rural Cambodia. A novel Biosensor, 'G6PD Standard' (SD Biosensor, Republic of Korea; Biosensor), can measure G6PD activity at the point of care. The objectives of this study were to compare the G6PD activity readings using Biosensors by village malaria workers (VMWs) and hospital-based laboratory technicians (LTs), and to compare the G6PD deficiency categorization recommended by the Biosensor manufacturer with categories derived from a locally estimated adjusted male median (AMM) in Kravanh district, Cambodia. Participants were enrolled between 2021 and 2022 in western Cambodia. Each of the 28 VMWs and 5 LTs received a Biosensor and standardized training on its use. The G6PD activities of febrile patients identified in the community were measured by VMWs; in a subset, a second reading was done by LTs. All participants were tested for malaria by rapid diagnostic test (RDT). The adjusted male median (AMM) was calculated from all RDT-negative participants and defined as 100% G6PD activity. VMWs measured activities in 1344 participants. Of that total, 1327 (98.7%) readings were included in the analysis, and 68 of these had a positive RDT result. We calculated 100% activity as 6.4 U/gHb (interquartile range: 4.5 to 7.8); 9.9% (124/1259) of RDT-negative participants had G6PD activities below 30%, 15.2% (191/1259) had activities between 30% and 70%, and 75.0% (944/1259) had activities greater than 70%. Repeat measurements among 114 participants showed a significant correlation of G6PD readings (rs = 0.784, p < 0.001) between VMWs and LTs. Based on the manufacturer's recommendations, 285 participants (21.5%) had less than 30% activity; however, based on the AMM, 132 participants (10.0%) had less than 30% activity. The G6PD measurements by VMWs and LTs were similar. With the provisions of training, supervision, and monitoring, VMWs could play an important role in the management of vivax malaria, which is critical for the rapid elimination of malaria regionally. Definitions of deficiency based on the manufacturer's recommendations and the population-specific AMM differed significantly, which may warrant revision of these recommendations.

Hypoxic Respiratory Failure Due to Pneumocystis Jiroveci and Cytomegalovirus Co-Infection in a Severely Immunocompromised Patient

Introduction:Immunocompromised individuals, such as those with HIV and low CD4 counts, are at increased risk for opportunistic infections. Although uncommon, these patients can be infected with multiple organisms, making diagnosis and management challenging for clinicians. Mortality remains high, as the data on initiating and adjusting antimicrobials when there is concern for co-infection is lacking. We present a case of Pneumocystis jiroveci (PCP) and cytomegalovirus (CMV) coinfection resulting in severe hypoxic respiratory failure and death. Case Report:A 38-year-old male with no past medical history presented with fever, dyspnea, and nonproductive cough. Vital signs were notable for a fever of 102.3°F, respiratory rate of 24, and oxygen saturation of 77% on room air. Physical examination revealed an ill-appearing male with bilateral rhonchi who became dyspneic with minimal conversation. Laboratory studies were significant for an elevated c-reactive protein, erythrocyte sedimentation rate, ferritin and lactate dehydrogenase. CT chest demonstrated bilateral ground glass opacities with multifocal consolidations. The patient was admitted for hypoxic respiratory failure secondary to suspected COVID pneumonia, despite negative testing. By hospital day 4, the patient had shown little improvement. Further work-up revealed that he was HIV positive with a CD4 count of 5, so he was empirically started on oral trimethoprim-sulfamethoxazole (TMPSMX) for presumed PCP pneumonia. On hospital day 9, the patient underwent endotracheal intubation for worsening hypoxia and subsequent bronchoscopy for further evaluation. PCP PCR confirmed the diagnosis, and the patient was transitioned to intravenous TMP-SMX. Still with minimal improvement, micafungin was added as potential salvage therapy. After 12 days of TMPSMX, treatment was changed to clindamycin/primaquine. CMV PCR from the bronchoalveolar lavage fluid came back positive at this time, so ganciclovir was added to the regimen. Despite multiple antimicrobials, the patient continued to decline. He was deemed not to be a candidate for ECMO given his profoundly immunocompromised status and ultimately died. Discussion:This case highlights the difficulties clinicians have in managing severely immunocompromised patients who worsen despite appropriate care. Little data exists providing guidelines on when to change to second and/or third-line agents in treating PCP pneumonia. Additionally, further studies need to be completed to delineate in whom empiric antimicrobials should be initiated early when co-infection is a possibility. ECMO may serve a purpose in this patient population given that lung rest is necessary to allow healing, but only a few cases of its use exist at this time.

In silico Drug Repurposing for the Identification of Antimalarial Drugs as Candidate Inhibitors of SARS-CoV-2

Background: Coronavirus disease (COVID-19) is a severe acute respiratory condition that has affected millions of people worldwide, indicating a global health emergency. Despite the deteriorating trends of COVID-19, no drugs are validated to have substantial efficacy in the potential treatment of COVID-19 patients in large-scale trials. Methods: This study aimed at identifying potential antimalarial candidate molecules for the treatment of COVID and evaluating the possible mechanism of action by in silico screening method. In silico screening studies on various antimalarial compounds, like amodiaquine, chloroquine, hydroxychloroquine, mefloquine, primaquine, and atovaquone, were conducted using PyRx and AutoDoc 1.5.6 tools against ACE 2 receptor, 3CL protease, hemagglutinin esterase, spike protein of SARS HR1 motif, and papain-like protease virus proteins. Results: Based on PyRx results, mefloquine and atovaquone were found to have higher docking affinity scores against virus proteins compared to other antimalarial compounds. Screening report of atovaquone exhibited affirmative inhibition constant for spike protein of SARS HR1 motif, 3CL protease, and papain-like protease. Conclusion: In silico analysis reported atovaquone as a promising candidate for COVID 19 therapy.