Suchergebnisse

Background: Malaria remains a critical public health problem in Southeast Asia despite intensive containment efforts. The continued spread of multi-drug-resistant Plasmodium falciparum has led to calls for malaria elimination on the Thai-Cambodian border. However, the optimal approach to elimination in difficult-to-reach border populations, such as the Military, remains unclear. Methods/design: A two-arm, cluster-randomized controlled, open-label pilot study is being conducted in military personnel and their families at focal endemic areas on the Thai-Cambodian border. The primary objective is to compare the effectiveness of monthly malaria prophylaxis (MMP) with dihydroartemisinin-piperaquine and weekly primaquine for 12 weeks compared with focused screening and treating (FSAT) following current Cambodian national treatment guidelines. Eight separate military encampments, making up approximately 1000 military personnel and their families, undergo randomization to the MMP or FSAT intervention for 3 months, with an additional 3 months' follow-up. In addition, each treatment cluster of military personnel and civilians is also randomly assigned to receive either permethrin- or sham (water)-treated clothing in single-blind fashion. The primary endpoint is risk reduction for malaria infection in geographically distinct military encampments based on their treatment strategy. Monthly malaria screening in both arms is done via microscopy, PCR, and rapid diagnostic testing to compare both the accuracy and cost-effectiveness of diagnostic modalities to detect asymptomatic infection. Universal glucose-6-phosphate dehydrogenase (G6PD) deficiency screening is done at entry, comparing the results from a commercially available rapid diagnostic test, the fluorescence spot test, and quantitative testing for accuracy and cost-effectiveness. The comparative safety of the interventions chosen is also being evaluated. Discussion: Despite the apparent urgency, the key operational elements of proposed malaria elimination strategies in Southeast Asian mobile and migrant populations, including the Military, have yet to be rigorously tested in a well-controlled clinical study. Here, we present a protocol for the primary evaluation of two treatment paradigms - monthly malaria prophylaxis and focused screening and treatment - to achieve malaria elimination in a Cambodian military population. We will also assess the feasibility and incremental benefit of outdoor-biting vector intervention - permethrin-treated clothing. In the process, we aim to define the cost-effectiveness of the inputs required for success including a responsive information system, skilled human resource and laboratory infrastructure requirements, and quality management. Despite being a relatively low transmission area, the complexities of multi-drug-resistant malaria and the movement of vulnerable populations require an approach that is not only technically sound, but simple enough to be achievable. Trial registration: ClinicalTrials.gov, ID: NCT02653898. Registered on 13 January 2016.

Southeast Asia (SEA) emerged relatively unscathed from the first year of the global SARS-CoV-2 pandemic, but as of July 2021 the region is experiencing a surge in case numbers primarily driven by Alpha (B.1.1.7) and subsequently the more transmissible Delta (B.1.617.2) variants. While initial disease burden was mitigated by swift government responses, favorable cultural and societal factors, the more recent rise in cases suggests an under-appreciation of prior prevalence and over-appreciation of possible cross-protective immunity from exposure to endemic viruses, and highlights the effects of vaccine rollout at varying tempos and of variable efficacy. This burgeoning crisis is further complicated by co-existence of malaria and dengue in the region, with implications of serological cross-reactivity on interpretation of SARS-CoV-2 assays and competing resource demands impacting efforts to contain both endemic and pandemic disease.

Dihydroartemisinin-piperaquine, the current first-line drug for uncomplicated malaria caused by Plasmodium falciparum and Plasmodium vivax in Cambodia, was previously shown to be of benefit as malaria chemoprophylaxis when administered as a monthly 3-day regimen. We sought to evaluate the protective efficacy of a compressed monthly 2-day treatment course in the Royal Cambodian Armed Forces. The safety and efficacy of a monthly 2-day dosing regimen of dihydroartemisinin-piperaquine were evaluated in a two-arm, randomized, double-blind, placebo-controlled cohort study with 2:1 treatment allocation. Healthy military volunteers in areas along the Thai-Cambodian border where there is a high risk of malaria were administered two consecutive daily doses of 180 mg dihydroartemisinin and 1,440 mg piperaquine within 30 min to 3 h of a meal once per month for a planned 4-month period with periodic electrocardiographic and pharmacokinetic assessment. The study was halted after only 6 weeks (69 of 231 projected volunteers enrolled) when four volunteers met a prespecified cardiac safety endpoint of QTcF (Fridericia's formula for correct QT interval) prolongation of >500 ms. The pharmacodynamic effect on the surface electrocardiogram (ECG) peaked approximately 4 h after piperaquine dosing and lasted 4 to 8 h. Unblinded review by the data safety monitoring board revealed mean QTcF prolongation of 46 ms over placebo at the maximum concentration of drug in serum (Cmax) on day 2. Given that dihydroartemisinin-piperaquine is one of the few remaining effective antimalarial agents in Cambodia, compressed 2-day treatment courses of dihydroartemisinin-piperaquine are best avoided until the clinical significance of these findings are more thoroughly evaluated. Because ECG monitoring is often unavailable in areas where malaria is endemic, repolarization risk could be mitigated by using conventional 3-day regimens, fasting, and avoidance of repeated dosing or coadministration with other QT-prolonging medications. (This study has been ...

Abstract Capacity-building initiatives related to public health are defined as developing laboratory infrastructure, strengthening host-country disease surveillance initiatives, transferring technical expertise and training personnel. These initiatives represented a major piece of the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) contributions to worldwide emerging infectious disease (EID) surveillance and response. Capacity-building initiatives were undertaken with over 80 local and regional Ministries of Health, Agriculture and Defense, as well as other government entities and institutions worldwide. The efforts supported at least 52 national influenza centers and other country-specific influenza, regional and U.S.-based EID reference laboratories (44 civilian, eight military) in 46 countries worldwide. Equally important, reference testing, laboratory infrastructure and equipment support was provided to over 500 field sites in 74 countries worldwide from October 2008 to September 2009. These activities allowed countries to better meet the milestones of implementation of the 2005 International Health Regulations and complemented many initiatives undertaken by other U.S. government agencies, such as the U.S. Department of Health and Human Services, the U.S. Agency for International Development and the U.S. Department of State.

Abstract Vector-borne infections (VBI) are defined as infectious diseases transmitted by the bite or mechanical transfer of arthropod vectors. They constitute a significant proportion of the global infectious disease burden. United States (U.S.) Department of Defense (DoD) personnel are especially vulnerable to VBIs due to occupational contact with arthropod vectors, immunological naiveté to previously unencountered pathogens, and limited diagnostic and treatment options available in the austere and unstable environments sometimes associated with military operations. In addition to the risk uniquely encountered by military populations, other factors have driven the worldwide emergence of VBIs. Unprecedented levels of global travel, tourism and trade, and blurred lines of demarcation between zoonotic VBI reservoirs and human populations increase vector exposure. Urban growth in previously undeveloped regions and perturbations in global weather patterns also contribute to the rise of VBIs. The Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) and its partners at DoD overseas laboratories form a network to better characterize the nature, emergence and growth of VBIs globally. In 2009 the network tested 19,730 specimens from 25 sites for Plasmodium species and malaria drug resistance phenotypes and nearly another 10,000 samples to determine the etiologies of non- Plasmodium species VBIs from regions spanning from Oceania to Africa, South America, and northeast, south and Southeast Asia. This review describes recent VBI-related epidemiological studies conducted by AFHSC-GEIS partner laboratories within the OCONUS DoD laboratory network emphasizing their impact on human populations.