Showing papers in "American Journal of Tropical Medicine and Hygiene in 2022"

Involvement of the Liver in COVID-19: A Systematic Review

Abstract: ABSTRACT. COVID-19, a respiratory viral infection, has affected 388 million individuals worldwide as of the February 4, 2022. In this review, we have outlined the important liver manifestations of COVID-19 and discussed the possible underlying pathophysiological mechanisms and their diagnosis and management. Factors that may contribute to hepatic involvement in COVID-19 include direct viral cytopathic effects, exaggerated immune responses/systemic inflammatory response syndrome, hypoxia-induced changes, vascular changes due to coagulopathy, endothelitis, cardiac congestion from right heart failure, and drug-induced liver injury. The majority of COVID-19-associated liver symptoms are mild and self-limiting. Thus management is generally supportive. Liver function tests and abdominal imaging are the primary investigations done in relation to liver involvement in COVID-19 patients. However, imaging findings are nonspecific. Severe acute respiratory syndrome coronavirus 2 RNA has been found in liver biopsies. However, there is limited place for liver biopsy in the clinical context, as it does not influence management. Although, the management is supportive in the majority of patients without previous liver disease, special emphasis is needed in those with nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, hepatitis B and C infections, and alcoholic liver disease, and in liver transplant recipients.

Preliminary Analysis of Excess Mortality in India During the COVID-19 Pandemic

Abstract: ABSTRACT. We studied all-cause mortality during the COVID-19 pandemic in 19 Indian states (population 1.27 billion). Excess mortality was calculated by comparison with years 2015 to 2019. The known COVID-19 deaths reported for a state were assumed to be accurate, unless excess mortality data suggested a higher toll. Data from one state were excluded due to anomalies. In several regions, fewer deaths were reported in 2020 than expected. Areas in Andhra Pradesh, Delhi, Haryana, Karnataka, Madhya Pradesh, Tamil Nadu, and West Bengal saw spikes in mortality in Spring 2021. The pandemic-related mortality through August 31, 2021, in 18 Indian states was estimated to be 198.7 per 100,000 population (range 146.1–263.8 per 100,000). If these rates apply nationally, then 2.69 million people (range 1.98 to 3.57 million) may have perished in India as a result of the pandemic by August 31, 2021.

Food Security, Conflict, and COVID-19: Perspective from Afghanistan

Abstract: ABSTRACT. Afghanistan, a country challenged by war and conflicts, has been in a state of turmoil for several years. The prolonged suffering has brought many challenges to the country’s inhabitants. Among these, food security is one important cause for concern. Food security occurs when people continuously have physical and economic access to adequate, safe, and nutritious food to meet their dietary requirements and food preferences for a functional and healthy life. Amid the pandemic, Afghanistan has witnessed a large increase in food shortages due to its dependence on neighboring countries. In light of current circumstances, food insecurity, coupled with political instability and the third wave of the COVID-19, have made it extremely hard for people to access daily provisions. Hence, people are left to navigate the COVID-19 pandemic with economic recession and poverty as the backdrop of the other health crises. To mitigate food security, international attempts are the required at this critical juncture. The aim of this article is to understand the causes leading to food insecurity and its implications in Afghanistan and to propose solutions that will improve the overall food security at the policy and implementation levels.

Making Statistical Sense of the Molnupiravir MOVe-OUT Clinical Trial

Abstract: ABSTRACT. Oral therapies for the early treatment of COVID-19 may prevent disease progression and health system overcrowding. A new oral therapeutic named molnupiravir has been promoted as providing an approximately 50% reduction in death or the need for hospitalization. The clinical trial evaluating this drug was stopped early at the recommendation of the Data Safety and Monitoring Board after approximately 50% of the sample had been recruited. At the point of discontinuing the trial, approximately 90% of the planned sample had been recruited and had available follow-up data accessible. We discuss issues about the study conduct, analysis, and interpretation, including 1) the authors and sponsors presented the interim analysis as the primary analysis; 2) communication between sponsors and the Data Safety and Monitoring Board was insufficient; 3) the treatment effects reverse when examining only the post-interim analysis population, and are substantially attenuated when examining the full data; 4) the choice of primary analysis is incorrect; 5) analysis of lost-to-follow-up patients favors the study drug; and 6) other known molnupiravir trials were not presented in the primary study findings. As a result of methodological and statistical concerns, it seems that external trials, separate from those supported by the sponsoring company, are required to determine the utility of this drug.

Fluvoxamine for the Early Treatment of COVID-19: A Meta-analysis of Randomized Clinical Trials

Abstract: ABSTRACT. Fluvoxamine is widely prescribed as an antidepressant. Recent studies show the drug may have a clinical benefit in treating COVID-19. We aimed to perform a meta-analysis of the existing randomized trials of fluvoxamine compared with placebo on the early treatment of COVID-19 patients. We included only randomized clinical trials enrolling ambulatory patients with early-stage disease (symptoms < 7 days) for the prevention of hospitalization. We searched MEDLINE and clinicaltrials.gov databases to identify trials and extract data with clarifications from the study investigators. We performed a fixed-effects meta-analysis and sensitivity analyses via R to evaluate the pooled estimate of hospitalization. We included three randomized trials: STOP COVID 1 and 2, and the TOGETHER Trial. The studies included a total of 2,196 patients. The STOP COVID trials measured clinical deterioration whereas the TOGETHER Trial measured hospitalization as the primary outcome. All trials reported on hospitalization up to day 28. The meta-analysis results show that patients receiving fluvoxamine were 31% less likely to experience clinical deterioration or hospitalization compared with placebo (risk ratio, 0.69; 95% CI, 0.54–0.88). A sensitivity analysis using the definition of hospitalization resulted in a risk reduction of 21% (95% CI, 0.60–1.03). Data from three randomized controlled trials show that fluvoxamine was associated with a reduction in the primary outcome measure (either clinical deterioration or composite outcome of hospitalization or extended emergency setting observation), although analysis of hospitalization-only was not statistically significant. More evidence from future trials is still needed to support the findings of this meta-analysis.

Multi-Dose Priming Regimens of PfSPZ Vaccine: Safety and Efficacy against Controlled Human Malaria Infection in Equatoguinean Adults

Abstract: ABSTRACT. Plasmodium falciparum sporozoite (PfSPZ) Vaccine is composed of radiation-attenuated, aseptic, purified cryopreserved PfSPZ. Multiple clinical trials empirically assessing two to six doses have shown multi-dose priming (two to four doses the first week) to be optimal for protection in both 4- and 16-week regimens. In this randomized, double-blind, normal saline (NS) placebo-controlled trial, four groups (G) of 18- to 32-year-old Equatoguineans received multi-dose priming regimens with or without a delayed final dose at 4 or 16 weeks. The regimens were G1: days 1, 3, 5, 7, and 113; G2: days 1, 3, 5, and 7; G3: days 1, 3, 5, 7, and 29; and G4: days 1, 8, and 29. All doses were 9 × 105 PfSPZ. Tolerability, safety, immunogenicity, and vaccine efficacy (VE) against homologous controlled human malaria infection (CHMI) 6–7 weeks after vaccination were assessed to down-select the best regimen. All four regimens were safe and well tolerated, with no significant differences in adverse events (AEs) between vaccinees (N = 84) and NS controls (N = 20) or between regimens. Out of 19 controls, 13 developed Pf parasitemia by quantitative polymerase chain reaction (qPCR) after CHMI. Only the vaccine regimen administered on study days 1, 8, and 29 gave significant protection (7/21 vaccinees versus 13/19 controls infected, VE 51.3%, P = 0.03, Barnard’s test, two-tailed). There were no significant differences in antibodies against Pf circumsporozoite protein (PfCSP), a major SPZ antigen, between protected and nonprotected vaccinees or controls pre-CHMI. The six controls not developing Pf parasitemia had significantly higher antibodies to blood stage antigens Pf exported protein 1 (PfEXP1) and Pf merozoite surface protein 1 (PfMSP1) than the controls who developed parasitemia, suggesting naturally acquired immunity against Pf limited infections in controls. This study identified a safe, protective, 4-week, multi-dose prime vaccination regimen for assessment in future trials of PfSPZ Vaccine.

Lessons from a Year of COVID-19 in Zambia: Reported Attendance and Mask Wearing at Large Gatherings in Rural Communities

Abstract: ABSTRACT. Zambia instituted prevention behavior guidelines for social gatherings before the first case of COVID-19 was confirmed on March 18, 2020. Guidelines included nonpharmaceutical interventions (NPIs) including mask wearing, social distancing, and reducing sizes of gatherings. Within a larger cluster randomized trial of community-based parenting groups in four rural districts (three in Southern Province, one in Eastern Province), we collected 5,711 questionnaires from intervention participants between August 2020 and September 2021, during which the country saw two COVID-19 waves. Questionnaires asked about participation and behaviors at community gatherings. Generally, perception of risk of contracting COVID-19 was low for respondents in districts in Southern Province but higher for those in Eastern Province. The highest compliance to mask wearing was reported at clinics (84%) and church services (81%), which were the most frequently attended gatherings. Many funerals were attended by 200 to 300 people, but individuals were 30% less likely to report wearing masks (odds ratio [OR] = 0.71, 95% confidence ratio [CI]: 0.6–0.8) than those attending a clinic visit. After controlling for other variables, the odds of self-reported mask wearing at events were higher in January to March 2021 (adjusted OR = 1.5, 95% CI: 1.3, 1.7) and July and September of 2021 (adjusted OR = 3.0, 95% CI: 2.5–3.5), timepoints that broadly overlay with two COVID-19 peaks observed in Zambia. Results suggest guideline dissemination penetrated the rural areas. However, there is need to optimize the messaging to increase compliance to NPIs at high-risk gatherings, including funerals. The findings from this analysis should be considered as the COVID-19 pandemic continues to evolve.

Neuroangiostrongyliasis: Global Spread of an Emerging Tropical Disease

Abstract: ABSTRACT. Neuroangiostrongyliasis (NAS) is an emerging parasitic disease caused by the neurotropic nematode Angiostrongylus cantonensis. Since it was first discovered, in rats in southern China in the 1930s, this tropical to subtropical parasite has spread to much of Southeast Asia, the Pacific Islands (including Hawaii), Australia, Japan, South America, the southeastern United States, the Caribbean, Africa, the Canary Islands, and the Balearic Islands. The parasite completes its natural life cycle in snails and slugs (intermediate hosts), and rats (definitive hosts). Humans become accidental hosts after ingesting infective third-stage larvae contained within uncooked or undercooked intermediate or paratenic hosts, an event that sometimes results in NAS, also known as rat lungworm disease. Although A. cantonensis larvae cannot complete their life cycle in humans, their migration into the brain and spinal cord combined with a powerful inflammatory reaction often leads to eosinophilic meningitis and can, in rare instances, lead to coma, paralysis, and death or, in other cases, chronic, disabling neurologic sequelae. Symptoms of NAS are diverse, which often makes it difficult to diagnose. Treatment may include administration of analgesics, corticosteroids, anthelminthics, and repeat lumbar punctures to reduce intracranial pressure. Unfortunately, few medical providers, even in endemic areas, are familiar with A. cantonensis or its epidemiology, diagnosis, and treatment. As the parasite continues to spread and NAS affects more people, medical practitioners, as well as the general public, must become more aware of this emerging zoonosis and the potentially devastating harm it can cause.

Lao Noma Survivors: A Case Series, 2002–2020

Abstract: ABSTRACT. Noma is a rapidly progressing infection of the oral cavity, mostly affecting children aged between 2 and 5 years. If untreated, mortality can reach 90% within a few weeks after the onset of symptoms. Most of the published literature on noma are case reports or case series from Africa. Studies including noma survivors in Asia are limited. We present a case series of noma survivors in Laos. A retrospective analysis of data collected to monitor the care provided to Lao noma survivors who presented for treatment from 2002 to 2020 was conducted. The review assessed data including sociodemographic characteristics, diagnosis, mouth opening, self-reported quality of life at admission and after surgery, and the names used for the disease. Of the 50 patients included, 25 (50%) were female. The median age of self-reported onset of acute noma was 4 years (interquartile range [IQR] 2–7 years). The noma survivors came from 14/17 (82%) of Lao provinces. There were 64 surgeries conducted on 45 of these survivors. There was a median of 25 years (IQR 16–33 years) between the time of acute infection and the provision of surgical care. Improvements in nutritional status and quality of life were evident after surgery. Patients referred to the disease as “Pak Phuey,” which means diseased mouth. Noma survivors frequently live for years with disabling sequelae. Surgical rehabilitation improves the quality of life for noma survivors.

Sensitive Diagnosis and Post-Treatment Follow-Up of Schistosoma mansoni Infections in Asymptomatic Eritrean Refugees by Circulating Anodic Antigen Detection and Polymerase Chain Reaction

Abstract: ABSTRACT. The increasing number of refugees coming from or passing through Schistosoma-endemic areas and arriving in Europe highlights the importance of screening for schistosomiasis on arrival, and focuses attention on the choice of diagnostic test. We evaluate the diagnostic performance of circulating anodic antigen (CAA) detection in 92 asymptomatic refugees from Eritrea. Results were compared with already-available stool microscopy, serology, and urine point-of-care circulating cathodic antigen (POC-CCA) data. For a full diagnostic comparison, real-time polymerase chain reaction (PCR) and the POC-CCA were included. All outcomes were compared against a composite reference standard. Urine and serum samples were subjected to the ultra-sensitive and highly specific up-converting particle lateral flow CAA test, Schistosoma spp. real-time PCR was performed on urine and stool, and the POC-CCA was used on urine using the G-score method. CAA was detected in 43% of urine and in 40% of serum samples. Urine PCR was negative in all 92 individuals, whereas 25% showed Schistosoma DNA in stool. POC-CCA was positive in 30% of individuals. The CAA test confirmed all microscopy positives, except for two cases that were also negative by all other diagnostic procedures. Post-treatment, a significant reduction in the number of positives and infection intensity was observed, in particular regarding CAA levels. Our findings confirm that microscopy, serology, and POC-CCA lack the sensitivity to detect all active Schistosoma infections. Accuracy of stool PCR was similar to microscopy, indicating that this method also lacks sensitivity. The CAA test appeared to be the most accurate method for screening active Schistosoma infections and for monitoring treatment efficacy.

High Prevalence of Asymptomatic Malarial Anemia and Association with Early Conversion from Asymptomatic to Symptomatic Infection in a Plasmodium falciparum Hyperendemic Setting in Cameroon

Abstract: ABSTRACT. Asymptomatic malarial parasitemia is highly prevalent in Plasmodium falciparum endemic areas and often associated with increased prevalence of mild to moderate anemia. The aim of this study was to assess the prevalence of anemia during asymptomatic malaria parasitemia and its interplay with persistent infection in highly exposed individuals. A household-based longitudinal survey was undertaken in a malaria hyperendemic area in Cameroon using multiplex nested polymerase chain reaction to detect plasmodial infections. Residents with P. falciparum asymptomatic parasitemia were monitored over a 3-week period with the aid of structured questionnaires and weekly measurements of axillary temperatures. Of the 353 individuals included (median age: 26 years, range 2–86 years, male/female sex ratio 0.9), 328 (92.9%) were positive for malaria parasitemia of whom 266 (81.1%) were asymptomatic carriers. The prevalence of anemia in the study population was 38.6%, of which 69.2% were asymptomatic. Multivariate analyses identified high parasitemia (> 327 parasites/µL) and female gender as associated risk factors of asymptomatic malarial anemia in the population. Furthermore, risk analyses revealed female gender and anemia at the time of enrolment as key predictors of early development of febrile illness (< 3 weeks post enrolment) among the asymptomatic individuals. Together, the data reveal an extremely high prevalence of asymptomatic malaria parasitemia and anemia in the study area, unveiling for the first time the association of asymptomatic malarial anemia with early clinical conversion from asymptomatic to symptomatic infection. Furthermore, these findings underscore the negative impact of asymptomatic malaria parasitemia on individual health, necessitating the development of appropriate control and preventive measures.

Proximity of Residence to Irrigation Determines Malaria Risk and Anopheles Abundance at an Irrigated Agroecosystem in Malawi

Abstract: ABSTRACT. As countries of sub-Saharan Africa expand irrigation to improve food security and foster economic growth, it is important to quantify the malaria risk associated with this process. Irrigated ecosystems can be associated with increased malaria risk, but this relationship is not fully understood. We studied this relationship at the Bwanje Valley Irrigation Scheme (800 hectares) in Malawi. Household prevalence of malaria and indoor Anopheles density were quantified in two cross-sectional studies in 2016 and 2017 (5,829 residents of 1,091 households). Multilevel logistic regression was used to estimate the association between distance to the irrigation scheme and malaria infection and mosquito density. The prevalence of malaria infection was 50.2% (2,765/5,511) by histidine-rich protein 2–based malaria rapid diagnostic tests and 30.1% (1,626/5,403) by microscopy. Individuals residing in households within 3 km of the scheme had significantly higher prevalence of infection (adjusted odds ratio [aOR] = 1.41; 95% confidence interval [CI] 1.18, 1.68); school-aged children had the highest prevalence among age groups (aOR = 1.34; 95% CI 1.11, 1.63). Individuals who reported bed net use, and households with higher socioeconomic status and higher level of education for household head or spouse, had lower odds of malaria infection. Female Anopheles mosquitoes (2,215 total; Anopheles arabiensis , 90.5%, Anopheles funestus , 9.5%) were significantly more abundant in houses located within 1.5 km of the scheme. Proximity of human dwellings to the irrigation scheme increased malaria risk, but higher household wealth index reduced risk. Therefore, multisectoral approaches that spur economic growth while mitigating increased malaria transmission are needed for people living close to irrigated sites.

Spatiotemporal Pattern of COVID-19–Related Mortality during the First Year of the Pandemic in Brazil: A Population-based Study in a Region of High Social Vulnerability

Abstract: ABSTRACT. Currently, the world is facing a severe pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Although the WHO has recommended preventive measures to limit its spread, Brazil has neglected most of these recommendations, and consequently, our country has the second largest number of deaths from COVID-19 worldwide. In addition, recent studies have shown the relationship between socioeconomic inequalities and the risk of severe COVID-19 infection. Herein, we aimed to assess the spatiotemporal distribution of mortality and lethality rates of COVID-19 in a region of high social vulnerability in Brazil (Northeast region) during the first year of the pandemic. A segmented log-linear regression model was applied to assess temporal trends of mortality and case fatality rate (CFR) and according to the social vulnerability index (SVI). The Local Empirical Bayesian Estimator and Global Moran Index were used for spatial analysis. We conducted a retrospective space–time scan to map clusters at high risk of death from COVID-19. A total of 66,358 COVID-19–related deaths were reported during this period. The mortality rate was 116.2/100,000 inhabitants, and the CFR was 2.3%. Nevertheless, CFR was > 7.5% in 27 municipalities (1.5%). We observed an increasing trend of deaths in this region (AMCP = 18.2; P = 0.001). Also, increasing trends were observed in municipalities with high ( N = 859) and very high SVI ( N = 587). We identified two significant spatiotemporal clusters of deaths by COVID-19 in this Brazilian region ( P = 0.001), and most high-risk municipalities were on the coastal strip of the region. Taken together, our analyses demonstrate that the pandemic has been responsible for several deaths in Northeast Brazil, with clusters at high risk of mortality mainly in municipalities on the coastline and those with high SVI.

Polymerase Chain Reaction-Based Malaria Diagnosis Can Be Increasingly Adopted during Current Phase of Malaria Elimination in India.

Abstract: Despite commendable progress in the control of malaria in India and other countries, there are hidden reservoirs of parasites in human hosts that continually feed malaria transmission. Submicroscopic infections are known to be a significant proportion in low-endemic settings like India and these infections do possess transmission potential. Hence, these reservoirs of infection add to the existing roadblocks for malaria elimination. It is crucial that this submerged burden of malaria is detected and treated to curtail further transmission. The currently used diagnostic tools including the so-called "gold standard" of microscopy are incapable of detecting these submicroscopic infections and thus are suboptimal. It is an opportune time to usher in more sensitive molecular tools like polymerase chain reaction (PCR) for routine diagnosis at all levels of healthcare as an additional diagnostic tool in routine settings. Polymerase chain reaction assays have been developed into user-friendly formats for field diagnostics and are near point of care. In India, because of the COVID-19 pandemic, these are being used rampantly across the country. The facilities created for COVID-19 diagnosis can easily be co-opted and harnessed for malaria diagnosis to augment surveillance by the inclusion of molecular techniques like PCR in the routine national malaria control program.

Ten Years of Universal Testing: How the Rapid Diagnostic Test Became a Game Changer for Malaria Case Management and Improved Disease Reporting

Abstract: In 2010, the World Health Organization changed its guidance on malaria case management, recommending parasitological confirmation of all suspected cases before treatment with an antimalarial. This recommendation was in large part as a result of the availability of quality assured malaria rapid diagnostic tests (RDTs) that made it possible for malaria diagnosis to be performed by laboratory staff in all health facilities irrespective of the facility's place in the tiered health system. Community health workers and other non-laboratory health workers who traditionally did not perform malaria testing due to the technical and logistic demands of smear microscopy were now able to test for malaria. The use of RDTs has led to substantial increases in testing rates, improved quality of case management, as well as more accurate reporting of malaria cases. Although current RDTs have limitations, they remain one of the most important tools in contemporary malaria control. Further improvements to existing products, such as increased sensitivity for non-falciparum tests, diversification of Plasmodium falciparum antigen targets, along with strengthened health system support for current RDTs will further enhance their utility in malaria control and prevention.

Understudied Anophelines Contribute to Malaria Transmission in a Low-Transmission Setting in the Choma District, Southern Province, Zambia

Abstract: ABSTRACT. Malaria transmission has declined substantially in Southern Province, Zambia, which is considered a low-transmission setting. The Zambian government introduced a reactive test-and-treat strategy to identify active zones of transmission and treat parasitemic residents. This study was conducted in the Choma District, Southern Province, Zambia, concurrently with an evaluation of this strategy to identify vectors responsible for sustaining transmission, and to identify entomological, spatial, and ecological risk factors associated with increased densities of mosquitoes. Anophelines were collected with CDC light traps indoors and near animal pens in index cases and neighboring households. Outdoor collections captured significantly more anophelines than indoor traps, and 10 different anopheline species were identified. Four species (Anopheles arabiensis, An. rufipes, An. squamosus, and An. coustani) were positive for Plasmodium falciparum circumsporozoite protein by ELISA, and 61% of these 26 anophelines were captured outdoors. Blood meal assays confirm plasticity in An. arabiensis foraging, feeding both on humans and animals, whereas An. rufipes, An. squamosus, and An. coustani were largely zoophilic and exophilic. Linear regression of count data for indoor traps revealed that households with at least one parasitemic resident by polymerase chain reaction testing was associated with higher female anopheline counts. This suggests that targeting households with parasitemic individuals for vector interventions may reduce indoor anopheline populations. However, many vectors species responsible for transmission may not be affected by indoor interventions because they are primarily exophilic and forage opportunistically. These data underscore the necessity for further evaluation of vector surveillance and control tools that are effective outdoors, in conjunction with current indoor-based interventions.

Characterizing Medicine Quality by Active Pharmaceutical Ingredient Levels: A Systematic Review and Meta-Analysis across Low- and Middle-Income Countries

Abstract: ABSTRACT. Substandard and falsified medicines are often reported jointly, making it difficult to recognize variations in medicine quality. This study characterized medicine quality based on active pharmaceutical ingredient (API) amounts reported among substandard and falsified essential medicines in low- and middle-income countries (LMICs). A systematic review and meta-analysis was conducted using PubMed, supplemented by results from a previous systematic review, and the Medicine Quality Scientific Literature Surveyor. Study quality was assessed using the Medicine Quality Assessment Reporting Guidelines (MEDQUARG). Random-effects models were used to estimate the prevalence of medicines with < 50% API. Among 95,520 medicine samples from 130 studies, 12.4% (95% confidence interval [CI]: 10.2–14.6%) of essential medicines tested in LMICs were considered substandard or falsified, having failed at least one type of quality analysis. We identified 99 studies that reported API content, where 1.8% (95% CI: 0.8–2.8%) of samples reported containing < 50% of stated API. Among all failed samples (N = 9,724), 25.9% (95% CI: 19.3–32.6%) reported having < 80% API. Nearly one in seven (13.8%, 95% CI: 9.0–18.6%) failed samples were likely to be falsified based on reported API amounts of < 50%, whereas the remaining six of seven samples were likely to be substandard. Furthermore, 12.5% (95% CI: 7.7–17.3%) of failed samples reported finding 0% API. Many studies did not present a breakdown of actual API amount of each tested sample. We offer suggested improved guidelines for reporting poor-quality medicines. Consistent data on substandard and falsified medicines and medicine-specific tailored interventions are needed to ensure medicine quality throughout the supply chain.

Case Report: A Fatal Case of Latent Melioidosis Activated by COVID-19

Abstract: ABSTRACT. Melioidosis, endemic in Southeast Asia and Northern Australia, is an uncommon but frequently fatal opportunistic infection caused by the Gram-negative saprophyte Burkholderia pseudomallei. We describe the first reported case of activation of latent melioidosis concurrent with COVID-19-associated lymphopenia and neutropenia in the setting of poorly controlled diabetes. A 43-year-old HIV-positive, diabetic man presented to the emergency department with persistent chills and progressive dyspnea. He was admitted for hypoxia. Chest X-ray showed bilateral parenchymal infiltrates suspicious for COVID-19. Shortly after admission, he became acutely encephalopathic, had a generalized seizure, and was transferred to the intensive care unit after intubation. Further workup showed severe neutropenia and lymphopenia. The patient received empiric antimicrobial coverage and was found to be severe acute respiratory syndrome coronavirus 2 positive. He deteriorated rapidly with refractory shock and persistent hypoxemia, and died 40 hours after admission. Blood cultures and sputum cultures obtained via bronchoalveolar lavage returned positive for Burkholderia pseudomallei. Given confirmed compliance with antiretrovirals, stable CD4 counts, and no recent foreign travel, the patient likely contracted the B. pseudomallei infection from travel to Southeast Asia many years prior and only became symptomatic after succumbing to severe acute respiratory syndrome coronavirus 2 infection. This case highlights the importance of considering activation of latent opportunistic infections by COVID-19 in immunocompromised patients.

Clinical and Molecular Epidemiology of Crimean-Congo Hemorrhagic Fever in Humans in Uganda, 2013–2019

Abstract: ABSTRACT. Crimean-Congo Hemorrhagic Fever (CCHF) is endemic in Uganda, yet its epidemiology remains largely uncharacterized. To better understand its occurrence within Uganda, case reports of patients hospitalized with CCHF between 2013 and 2019 were reviewed. Further, genome sequences of CCHF-positive RNA obtained during this period were determined for phylogenetic comparisons. We found that a total of 32 cases (75% males; CFR, 31.2%), aged between 9 to 68 years, were reported during the study period. Most cases were detected during July to December of each outbreak year (81.2%; P < 0.01) and were located along the “cattle corridor” (68.7%, P = 0.03). The most common presenting symptoms were fever (93.8%), hemorrhage (81.3%), headache (78.1%), fatigue (68.8%), vomiting (68.8%), and myalgia (65.6%). In five patients for whom hematological data were available, varied abnormalities were observed including thrombocytopenia, leukopenia, anemia, lymphopenia, lymphocytosis, polycythemia, and microcytosis. About 56.3% ( P = 0.47) of patients reported tick bites or exposure to livestock as their potential source of infection. Person-to-person transmission was suspected for two cases. Using unbiased metagenomics, we found that the viral S- and L- segments have remained conserved in Africa 2 clade since the 1950s. In contrast, the M segment split into two geographically interspersed clades; one that belongs to Africa 2 and another that is ancestral to Africa 1 and 2. Overall, this data summarizes information on the history and clinical presentation of human CCHF in Uganda. Importantly, it identifies vulnerable populations as well as temporal and geographic regions in Uganda where surveillance and control interventions could be focused.

Pfs47 as a Malaria Transmission-Blocking Vaccine Target.

Abstract: Transmission-blocking vaccines (TBVs), pioneered by Richard Carter and others, aim to prevent parasite development in the mosquito vector and are a promising new tool for malaria elimination. Pfs47, recently identified as a TBV target, is a three-domain 6-cysteine protein on the surface of Plasmodium falciparum sexual stages. Pfs47 allows the parasite to evade mosquito immunity and is key for P. falciparum infection of the dominant malaria vectors Anopheles gambiae, Anopheles dirus, and Anopheles albimanus. Antibodies against Pfs47 domain 2 (D2) have significant transmission-blocking activity that prevents Plasmodium ookinete development and is independent of human complement. Strong transmission-blocking activity has been mapped to a region of 52 amino acids in Pfs47 D2. Efforts to optimize the immunogenicity of the Pfs47 D2 antigen with a viral-like particle have been successful, and the efficacy of a P47-based TBV was confirmed in vivo with Pbs47, the orthologue of Pfs47 in the mouse malaria parasite Plasmodium berghei. The current evidence warrants further development and clinical testing of a Pfs47-based TBV.

Incidence Estimates of Acute Q Fever and Spotted Fever Group Rickettsioses, Kilimanjaro, Tanzania, from 2007 to 2008 and from 2012 to 2014

Abstract: Q fever and spotted fever group rickettsioses (SFGR) are common causes of severe febrile illness in northern Tanzania. Incidence estimates are needed to characterize the disease burden. Using hybrid surveillance-coupling case-finding at two referral hospitals and healthcare utilization data-we estimated the incidences of acute Q fever and SFGR in Moshi, Kilimanjaro, Tanzania, from 2007 to 2008 and from 2012 to 2014. Cases were defined as fever and a four-fold or greater increase in antibody titers of acute and convalescent paired sera according to the indirect immunofluorescence assay of Coxiella burnetii phase II antigen for acute Q fever and Rickettsia conorii (2007-2008) or Rickettsia africae (2012-2014) antigens for SFGR. Healthcare utilization data were used to adjust for underascertainment of cases by sentinel surveillance. For 2007 to 2008, among 589 febrile participants, 16 (4.7%) of 344 and 27 (8.8%) of 307 participants with paired serology had Q fever and SFGR, respectively. Adjusted annual incidence estimates of Q fever and SFGR were 80 (uncertainty range, 20-454) and 147 (uncertainty range, 52-645) per 100,000 persons, respectively. For 2012 to 2014, among 1,114 febrile participants, 52 (8.1%) and 57 (8.9%) of 641 participants with paired serology had Q fever and SFGR, respectively. Adjusted annual incidence estimates of Q fever and SFGR were 56 (uncertainty range, 24-163) and 75 (uncertainty range, 34-176) per 100,000 persons, respectively. We found substantial incidences of acute Q fever and SFGR in northern Tanzania during both study periods. To our knowledge, these are the first incidence estimates of either disease in sub-Saharan Africa. Our findings suggest that control measures for these infections warrant consideration.

Impact of Annual versus Semiannual Mass Drug Administration with Ivermectin and Albendazole on Helminth Infections in Southeastern Liberia

Abstract: We compared the impact of three rounds of annual and five rounds of semiannual mass drug administration (MDA) with albendazole plus ivermectin on helminthic infections in Liberia. Repeated annual cross-sectional community surveys were conducted between 2013 and 2019 in individuals of 5 years and older. Primary outcome was the change of infection prevalence estimates from baseline to month 36 (12 months after the last treatment). After three rounds of annual MDA, Wuchereria bancrofti circulating filarial antigen (CFA) and microfilaria (Mf) prevalence estimates decreased from 19.7% to 4.3% and from 8.6% to 0%, respectively; after semiannual MDA, CFA and Mf prevalences decreased from 37.8% to 16.8% and 17.9% to 1%, respectively. Mixed effects logistic regression models indicated that the odds of having Mf decreased by 97% (P < 0.001) at month 36 (similar odds for annual and semiannual MDA zones). A parallel analysis showed that the odds of CFA were reduced by 83% and 69% at 36 months in the annual and semiannual treatment zones, respectively (P < 0.001). Onchocerca volvulus Mf prevalence decreased slightly after multiple MDA rounds in both treatment zones. Reductions in hookworm and Trichuris trichiura prevalences and intensities were slightly greater in the annual treatment zone. Ascaris lumbricoides prevalence rates were relatively unchanged, although infection intensities decreased sharply throughout. Results show that annual and semiannual MDA were equally effective for reducing LF and soil-transmitted helminth infection parameters over a 3-year period, and reductions recorded at month 36 were sustained by routine annual MDA through month 72.

The Dominance of Severe Acute Respiratory Syndrome Coronavirus 2 B.1.617 and Its Sublineages and Associations with Mortality during the COVID-19 Pandemic in India between 2020 and 2021

Abstract: ABSTRACT. As the COVD-19 pandemic spreads, several new severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) variants with various mutations across the genome have arisen, and they appear to be the greater risk to global public health. In this study, we have performed molecular characterization of SARS-COV-2 circulating in India between January 2020 and May 2021. Phylogenetic analysis of the SARS-COV-2 reported in the first and second waves of the outbreak showed the evolutionary hierarchy of SARS-COV-2 that was dispersed across the evolutionary tree of SARS-COV-2 with six major next strain clades: 19A (5.3%), 20A (29.9%), 20B (24.9%), 20I-Alpha, V1 (7.4%), 21A-Delta (17.2%), and 21B-Kappa (12.7%). Among the observed clades, 21A-Delta and 21B-Kappa belonging to the B.1.617 and its sublineages are the two notable clades that dominated approximately 78% of the total SARS-COV-2 genomes reported during April and May 2021. This study has also established a link between different SARS-COV-2 variants and risk of mortality during the COVID-19 epidemic using multivariable logistic regression model for patient-level data. The estimated model demonstrates that the risk of mortality of the COVID 19 patients infected by variant B.1.617 and/or its sublineages is much higher than the other preexisting SARS-COV-2 variants, especially among individuals over 45 years of age, regardless of gender. Considering the transmissibility of the B.1.617 and its sublineages and its potential impact to the public health, real-time analysis of COVID-19 cases coupled with stringent genomics surveillance are promising tools to develop and adapt stringent measures to contain and reduce the impact of SARS-COV-2.

Case Report: Cambodian National Malaria Surveillance Program Detection of Plasmodium knowlesi

Abstract: ABSTRACT. Despite recent success in reducing the regional incidence of Plasmodium falciparum malaria, cases of zoonotic malaria are on the rise in Southeast Asia. The Cambodian National Malaria Surveillance Program has previously relied on rapid diagnostic tests and blood smear microscopy with confirmatory polymerase chain reaction (PCR) testing in a subset of cases to further distinguish P. falciparum, P. malariae, P. ovale, and P. vivax species. Here, metagenomic next-generation sequencing identified P. knowlesi mono-infection in six Cambodian patients initially diagnosed with P. malariae by blood smear microscopy in February–May 2020. These findings of recent human infections with P. knowlesi in Cambodia led to the incorporation of P. knowlesi–specific PCR diagnostics to national malaria surveillance efforts.

Melioidosis: Laboratory Investigations and Association with Patient Outcomes

Abstract: ABSTRACT. Melioidosis is an infection caused by the bacterium Burkholderia pseudomallei . The most common presentation is bacteremia occurring in 38–73% of all patients, and the mortality rate ranges from 9% to 42%. Although there is abundant data representing risk factors for infection and patient outcomes, there is limited information regarding laboratory investigations associated with bacteremia and mortality. We assessed a range of baseline and diagnostic investigations and their association with patient outcomes in a retrospective cohort study in Townsville, Australia. 124 patients’ medical and laboratory records were reviewed between January 1, 1997 and December 31, 2020. Twenty-seven patients died and 87 patients were bacteremic. The presence of lymphopenia (< 1.5 × 10 9 cells/L) was the highest risk for bacteremia (relative risk [RR] 2.2; 95% CI: 1.3–3.7, P < 0.001). Factors associated with mortality included lymphopenia, (RR: 1.4; 95% CI: 1.2–1.6, P = 0.004); uremia (RR: 1.7; 95% CI: 1.1–2.5, P = 0.03); and an elevated international normalized ratio (RR: 1.5; 95% CI: 1.2–2.0, P = 0.006). Median incubation to positive blood culture result was 28 hours with 15/82 (18%) positive in ≤ 24 hours. For serological testing during admission only 53/121 (44%) were indirect hemagglutination assay positive, 67/120 (56%) enzyme immunoassay IgG positive, and 23/89 (26%) IgM positive. Simple baseline investigations at time of presentation may be used to stratify patients at high risk for both bacteremia and mortality. This information can be used as a decision aid for early intensive management.

Q Fever as a Cause of Community-Acquired Pneumonia in French Guiana

Abstract: ABSTRACT. In French Guiana, community-acquired pneumonia (CAP) represents over 90% of Coxiella burnetii acute infections. Between 2004 and 2007, we reported that C. burnetii was responsible for 24.4% of the 131 CAP hospitalized in Cayenne. The main objective of the present study was to determine whether the prevalence of Q fever pneumonia remained at such high levels. The secondary objectives were to identify new clinical characteristics and risk factors for C. burnetii pneumonia. A retrospective case-control study was conducted on patients admitted in Cayenne Hospital, between 2009 and 2012. All patients with CAP were included. The diagnosis of acute Q fever relied on titers of phase II IgG ≥ 200 and/or IgM ≥ 50 or seroconversion between two serum samples. Patients with Q fever were compared with patients with non-C. burnetii CAP in bivariate and multivariate analyses. During the 5-year study, 275 patients with CAP were included. The etiology of CAP was identified in 54% of the patients. C. burnetii represented 38.5% (106/275; 95% CI: 31.2–45.9%). In multivariate analysis, living in Cayenne area, being aged 30–60 years, C-reactive protein (CRP) > 185 mg/L, and leukocyte count < 10 G/L were independently associated with Q fever. The prevalence of Q fever among CAP increased to 38.5%. This is the highest prevalence ever reported in the world. This high prevalence justifies the systematic use of doxycycline in addition to antipneumococcal antibiotic regimens.

Talaromyces marneffei Influences Macrophage Polarization and Sterilization Ability via the Arginine Metabolism Pathway in Vitro

Abstract: ABSTRACT. The opportunistic fungal pathogen Talaromyces marneffei, which is endemic across a narrow band of tropical Southeast Asia and southern China, is an intracellular pathogen that causes systemic and lethal infection through the mononuclear phagocyte system. The mechanisms by which T. marneffei successfully replicates and escapes the immune system remain unclear. To investigate the role of arginine metabolism in the escape of T. marneffei from killer macrophages, we assessed inducible nitric oxide synthase (iNOS) and arginase expression, nitric oxide (NO) production, arginase and phagocytic activity, and the killing of T. marneffei in a coculture system. Our results indicate that T. marneffei induced macrophage polarization toward the M2 phenotype and regulated the arginine metabolism pathway by prolonging infection, thereby reducing antimicrobial activity and promoting fungal survival. Moreover, inhibiting T. marneffei–induced macrophage arginase activity with Nω-hydroxy-nor-arginine restored NO synthesis and strengthened fungal killing. These findings indicate that T. marneffei affects macrophage polarization and inhibits macrophage antimicrobial function via the arginine metabolism pathway.

Immunogenicity of Oxford-AstraZeneca COVID-19 Vaccine in Vietnamese Health-Care Workers

Abstract: ABSTRACT. We studied the immunogenicity of the Oxford-AstraZeneca vaccine in health-care workers of a major infectious diseases hospital in Vietnam. We measured neutralizing antibodies before and 14 days after each dose, and at day 28 and month 3 after dose 1. A total of 554 workers (136 men and 418 women; age range, 22–71 years; median age, 36 years) participated with the study. Of the 144 participants selected for follow-up after dose 1, 104 and 94 gave blood for antibody measurement at weeks 6 and 8, and at month 3 after dose 1, respectively. The window time between the two doses was 6 weeks. At baseline, none had detectable neutralizing antibodies. After dose 1, the proportion of participants with detectable neutralizing antibodies increased from 27.3% (151 of 554) at day 14 to 78.0% (432 of 554) at day 28. Age correlated negatively with the development and the levels of neutralizing antibodies. However, at day 28, these differences were less profound, and women had a greater seroconversion rate and greater levels of neutralizing antibodies than men. After dose 2, these age and gender associations were not observable. In addition, the proportion of study participants with detectable neutralizing antibodies increased from 70.2% (73 of 104) before dose 2 (week 6, after dose 1) to 98.1% (102 of 104) 14 days later. At month 3, neutralizing antibodies decreased and 94.7% (89 of 94) of the study participants remained seropositive. The Oxford-AstraZeneca COVID-19 vaccine is immunogenic in Vietnamese health-care workers. These data are critical to informing the deployment of the COVID-19 vaccine in Vietnam and in Southeast Asia, where vaccination coverage remains inadequate.

Public Perceptions, More Than Misinformation, Explain Poor Adherence to Proven COVID-19 Control Measures

Abstract: ABSTRACT. Since the beginning of the COVID-19 pandemic, there has been a profusion of studies and webinars on the infodemic (the rapid diffusion of information on the internet). The infodemic is often cited as a key factor in the lack of adherence to COVID-19 preventive measures, including vaccination. A study we conducted in West Africa questions the reality of this impact: the majority of people who do not adhere to the preventive measures draw their opinion from their own experience, not from what they have viewed or read on social networks. Historically, resistance to public health messages and interventions, including vaccination, existed before the advent of the Internet. Studying the perceptions of the population and not only the circulation of information is necessary to fully understand the lack of adherence to the COVID-19 preventive measures and to build an effective communication strategy.

COVID-19 Community Transmission and Super Spreaders in Rural Villages from Manabi Province in the Coastal Region of Ecuador Assessed by Massive Testing of Community-Dwelling Population

Abstract: ABSTRACT. Neglected rural communities in Latin America are highly vulnerable to COVID-19 due to a poor health infrastructure and limited access to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis. Manabí is a province of the Coastal Region of Ecuador characterized by a high prevalence of rural population living under poverty conditions. In the current study, we present the retrospective analysis of the results of a massive SARS-CoV-2 testing operation in nonhospitalized populations from Manabí carried out from August to September 2020. A total of 4,003 people from 15 cantons were tested for SARS-CoV-2 by reverse-transcriptase quantitative polymerase chain reaction, resulting in an overall infection rate of 16.13% for SARS-CoV-2, with several communities > 30%. Moreover, 29 SARS-CoV-2 super-spreader community-dwelling individuals with viral loads above 10 8 copies/mL were found. These results support that uncontrolled COVID-19 community transmission was happening in Manabí during the first semester of COVID-19 pandemic. This report endorses the utility of massive SARS-CoV-2 testing among asymptomatic population for control and surveillance of COVID-19.