The American Journal of Tropical Medicine and Hygiene - Current Issue

Fifteen years of investment in malaria control on Bioko Island, Equatorial Guinea (EG), dramatically reduced malaria-associated morbidity and mortality, but the impact has plateaued. To progress toward elimination, EG is investing in the development of a malaria vaccine. We assessed the unique public–private partnership that has had such a significant impact on malaria on Bioko Island and now added a major effort on malaria vaccine development. As part of a $79M commitment, the EG government (75%) and three American energy companies (25%) have invested since 2012 greater than $55M in the Equatoguinean Malaria Vaccine Initiative (EGMVI) to support clinical development of Sanaria® PfSPZ vaccines (Sanaria Inc., Rockville, MD). In turn, the vaccine development program is building human capital and physical capacity. The EGMVI established regulatory and ethical oversight to ensure compliance with the International Conference on Harmonization and Good Clinical Practices for the first importation of investigational product, ethical approval, and conduct of a clinical trial in Equatoguinean history. The EGMVI has completed three vaccine trials in EG, two vaccine trials in Tanzania, and a malaria incidence study, and initiated preparations for a 2,100-volunteer clinical trial. Personnel are training for advanced degrees abroad and have been trained in Good Clinical Practices and protocol-specific methods. A new facility has established the foundation for a national research institute. Biomedical research and development within this visionary, ambitious public–private partnership is fostering major improvements in EG. The EGMVI plans to use a PfSPZ Vaccine alongside standard malaria control interventions to eliminate Pf malaria from Bioko, becoming a potential model for elimination campaigns elsewhere.

The COVID-19 pandemic is among the deadliest infectious diseases to have emerged in recent history. As with all past pandemics, the specific mechanism of its emergence in humans remains unknown. Nevertheless, a large body of virologic, epidemiologic, veterinary, and ecologic data establishes that the new virus, SARS-CoV-2, evolved directly or indirectly from a β-coronavirus in the sarbecovirus (SARS-like virus) group that naturally infect bats and pangolins in Asia and Southeast Asia. Scientists have warned for decades that such sarbecoviruses are poised to emerge again and again, identified risk factors, and argued for enhanced pandemic prevention and control efforts. Unfortunately, few such preventive actions were taken resulting in the latest coronavirus emergence detected in late 2019 which quickly spread pandemically. The risk of similar coronavirus outbreaks in the future remains high. In addition to controlling the COVID-19 pandemic, we must undertake vigorous scientific, public health, and societal actions, including significantly increased funding for basic and applied research addressing disease emergence, to prevent this tragic history from repeating itself.

The world is currently facing a novel COVID-19 pandemic caused by SARS-CoV-2 that, as of July 12, 2020, has caused a reported 12,322,395 cases and 556,335 deaths. To date, only two treatments, remdesivir and dexamethasone, have demonstrated clinical efficacy through randomized controlled trials (RCTs) in seriously ill patients. The search for new or repurposed drugs for treatment of COVID-19 continues. We have witnessed anecdotal use of herbal medicines, including Artemisia spp. extracts, in low-income countries, and exaggerated claims of their efficacies that are not evidence based, with subsequent political controversy. These events highlight the urgent need for further research on herbal compounds to evaluate efficacy through RCTs, and, when efficacious compounds are identified, to establish the active ingredients, develop formulations and dosing, and define pharmacokinetics, toxicology, and safety to enable drug development. Derivatives from the herb Artemisia annua have been used as traditional medicine over centuries for the treatment of fevers, malaria, and respiratory tract infections. We review the bioactive compounds, pharmacological and immunological effects, and traditional uses for Artemisia spp. derivatives, and discuss the challenges and controversies surrounding current efforts and the scientific road map to advance them to prevent or treat COVID-19.

Use of medical masks is a key strategy for COVID-19 prevention among healthcare workers. Unfortunately, there are global shortages of this essential commodity, and many have resulted in inappropriate usage to conserve supply. This article highlights the likely benefits of face mask containers in promoting safe, appropriate, and extended use of medical masks by healthcare workers in settings where a sustainable supply of medical masks may be limited.

In the United States, Chagas disease is diagnosed in less than 1% of the estimated > 300,000 people who have the disease. However, the actual prevalence remains unknown, and these estimates may be wide of the mark (too high or too low). The greater part of those living with the disease acquired the infection in an endemic region of Latin America, but autochthonous transmission in the United States is increasingly being described. These cases are considered rare, and the transmission routes are largely unknown. Although triatomines or “kissing bugs” harbor Trypanosoma cruzi in North America, most autochthonous cases are presumed rather than confirmed exposures to naturally infected kissing bugs. Public knowledge of Chagas is growing, and efforts are underway to provide greater awareness, but what are the risk factors for human transmission of Chagas disease in the United States?

Nine criteria regarding the infectious agent, mode of transmission, portal of entry, route of spread, target organs, target cells, pathologic lesions, incubation period, and modifiable spectrum of disease and outcomes appropriate to the intended experimental purpose are described. To provide context for each criterion, mouse models of two vector-borne zoonotic infectious diseases, scrub typhus and dengue, are summarized. Application of the criteria indicates that intravenous inoculation of Orientia tsutsugamushi into inbred mice is the best current model for life-threatening scrub typhus, and intradermal inoculation accurately models sublethal human scrub typhus, whereas the immunocompromised mouse models of dengue provide disease outcomes most closely associated with human dengue. In addition to addressing basic questions of immune and pathogenic mechanisms, mouse models are useful for preclinical testing of experimental vaccines and therapeutics. The nine criteria serve as guidelines to evaluate and compare models of vector-borne infectious diseases.

Gene drive technologies represent powerful tools to develop vector control strategies that will complement the current approaches to mitigate arthropod-borne infectious diseases. The characteristics of gene drive technologies have raised additional concerns to those for standard genetically engineered organisms. This generates a need for adaptive governance that has not been met yet because of the rapid rate of progress in gene drive research. For the eventual release of gene drive insects into wild populations, an international governance network would be helpful in guiding scientists, stakeholders, public opinion, and affected communities in its use. We examined the current institutions and governing bodies among various continents that could have an impact on gene drive governance or the potential to adapt to its future use. Possible governance strategies also are proposed that seek to bridge gaps and promote an ethically sound policy framework. Ideally, governance strategies should be developed before or at the same pace as gene drive research to anticipate field releases and maximize their impact as a public health tool. However, this is not likely to happen as it takes years to develop global accords, and some countries may choose to move ahead independently on the new technology.

Quality of care is essential for improving health outcomes, but heterogeneity in theoretical frameworks and metrics can limit studies’ generalizability and comparability. This research aimed to compare definitions of care quality across research articles that incorporate data from Service Provision Assessment (SPA) surveys. Following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, we used a keyword search in PubMed. Each author reviewed abstracts, then full texts, for inclusion criteria, and peer-reviewed publications of empirical analysis using SPA data. The search yielded 3,250 unique abstracts, and 34 publications were included in the final analysis. We extracted details on the SPA dataset(s) used, theoretical framework applied, and how care quality was operationalized. The 34 included articles used SPA data from 14 surveys in nine countries (all in sub-Saharan Africa plus Haiti). One-third of these articles (n = 13) included no theoretical or conceptual framework for care quality. Among those articles referencing a framework, the most common was the Donabedian model (n = 7). Studies operationalized quality constructs in extremely different ways. Few articles included outcomes as a quality construct, and the operationalization of structure varied widely. A key asset of SPA surveys, owing to the standardized structure and use of harmonized data collection instruments, is the potential for cross-survey comparisons. However, this is limited by the lack of a common framework for measuring and reporting quality in the existing literature using SPA data. Service Provision Assessment surveys offer unique and valuable insights, and a common framework and approach would substantially strengthen the body of knowledge on quality of care in low-resource settings.

The COVID-19 pandemic has proved to be an enormous challenge to the health of the world population with tremendous consequences for the world economy. New knowledge about COVID-19 is being acquired continuously. Although the main manifestation of COVID-19 is SARS, dysfunction in other organs has been described in the last months. Neurological aspects of COVID-19 are still an underreported subject. However, a plethora of previous studies has shown that human CoVs might be neurotropic, neuroinvasive, and neurovirulent, highlighting the importance of this knowledge by physicians. Besides, several neurological manifestations had been described as complications of two other previous outbreaks of CoV diseases (SARS ad Middle East respiratory syndrome). Therefore, we should be watchful, searching for early evidence of neurological insults and promoting clinical protocols to investigate them. Our objectives are to review the potential neuropathogenesis of this new CoV and the neurological profile of COVID-19 patients described so far.

A 1-year population-based prospective study was launched in Seychelles, a country with one of the highest human incidence of leptospirosis worldwide, to describe the characteristic features of the epidemiology of the disease and highlight the most prominent risk factors. Diagnosis was based on the IgM enzyme-linked immunosorbent assay, microscopic agglutination test, and real-time PCR. A standardized questionnaire was administered to 219 patients aged ≥ 13 years consulting for acute febrile illness. The high incidence of leptospirosis in Seychelles was confirmed. The disease was particularly severe, as the case fatality rate was 11.8%. Leptospirosis was positively associated in univariate analysis with socio-professional and clinical variables including gardening/farming, oliguria, jaundice, conjunctivitis, history of hepatitis C virus infection, anemia, thrombocytopenia, and/or biological renal failure. Epidemiological analyses of the questionnaires highlighted a link of the disease with living in houses (versus apartment), the presence of animals around and in houses, gardening, and misuse of personal protective equipment. Multivariate analyses indicated that being a farmer/landscaper and having cattle and cats around the home are the most significant drivers of leptospirosis. Biological features most associated with leptospirosis were thrombocytopenia, leukocytosis, high values for renal function tests, and elevated total bilirubin. We report changes in behavior and exposure compared with data collected on leptospirosis 25 years ago, with indication that healthcare development has lowered case fatality. Continuous health education campaigns are recommended as well as further studies to clarify the epidemiology of human leptospirosis, especially the role of domestic animals.

For the last decade, the New Jersey (NJ) Department of Health has reported between 42 and 144 new cases each year of “spotted fever group rickettsiosis” (SFGR), a statistic that reflects uncertainty regarding which rickettsial agents (Proteobacteria: Rickettsiaceae: Rickettsia) are infecting NJ residents. To identify the Rickettsia circulating in NJ ticks, we used a combination of conventional and real time PCR approaches to screen 560 Dermacentor variabilis Say and 245 Amblyomma americanum L. obtained from a 1-day state-wide surveillance in May 2018 and an additional 394 D. variabilis collected across NJ in 2013–2018. We found zero D. variabilis infected with Rickettsia rickettsii, the agent of Rocky Mountain spotted fever and, on average, 1.3% infected with presumed nonpathogenic Rickettsia montanensis. We also found zero A. americanum infected with R. rickettsii, and 20% infected with Rickettsia amblyommatis, a prevalence somewhat lower than in more southern states. Overall, we conclude that it is unlikely that R. rickettsii vectored by D. variabilis is a primary cause of SFGR cases in NJ and discuss our findings in the context of known facts and current limitations. We conclude that understanding the causes of SFGR east of the Mississippi will require collaboration among medical doctors, public health authorities, and medical entomologists to follow up presumptive human cases of SFGR with detailed histories of exposure, species-specific molecular assays, and active surveillance of putative vectors and the pathogens they may carry.

Murine typhus is a flea-borne rickettsiosis caused by Rickettsia typhi. When severe, endothelial dysfunction can lead to acute kidney injury secondary to prerenal azotemia or acute tubular necrosis. Here, we describe an unusual cause of kidney injury during the course of murine typhus–focal segmental glomerulosclerosis.

Typhoid fever transmission occurs through ingestion of food or water contaminated with Salmonella Typhi, and case–control studies are often conducted to identify outbreak sources and transmission vehicles. However, there is no current summary of the associations among water, sanitation, and hygiene (WASH); and food exposures and typhoid from case–control studies. We conducted a systematic review and meta-analysis of case–control studies to evaluate the associations among typhoid fever and predicted WASH or food exposure risk factors (13), and protective factors (7). Overall, 19 manuscripts describing 22 case–control studies were included. Two studies were characterized as having low risk of bias, one as medium risk, and 19 as high risk. In total, nine of 13 predicted risk factors were associated with increased odds of typhoid (odds ratio [OR] = 1.4–2.4, I 2 = 30.5–74.8%.), whereas five of seven predicted protective factors were associated with lower odds of typhoid (OR = 0.52–0.73, I 2 = 38.7–84.3%). In five types of sensitivity analyses, two (8%) of 26 summary associations changed significance from the original analysis. Results highlight the following: the importance of household hygiene transmission pathways, the need for further research around appropriate food interventions and the risk of consuming specific foods and beverages outside the home, and the absence of any observed association between sanitation exposures and typhoid fever. We recommend that typhoid interventions focus on interrupting household transmission routes and that future studies provide more detailed information about WASH and food exposures to inform better targeted interventions.

Transcutaneous vaccination can induce both mucosal and systemic immune responses. However, there are few data on anti-polysaccharide responses following transcutaneous vaccination of polysaccharides, despite the role that anti-polysaccharide responses play in protecting against intestinal mucosal and respiratory pathogens. Whether transcutaneous vaccination with a conjugate polysaccharide vaccine would be able to induce memory responses is also unknown. To address this, we transcutaneously vaccinated mice with virulence antigen (Vi) polysaccharide of Salmonella enterica serovar Typhi (the cause of typhoid fever), either in unconjugated or conjugated form (the latter as a Vi-DT conjugate). We also assessed the ability of the immunoadjuvant cholera toxin to impact responses following vaccination. We found that presenting Vi in a conjugate versus nonconjugate form transcutaneously resulted in comparable serum IgG responses but higher serum and lamina propria lymphocyte IgA anti-Vi responses, as well as increased IgG memory responses. The addition of immunoadjuvant did not further increase these responses; however, it boosted fecal IgA and serum IgG anti-Vi responses. Our results suggest that transcutaneous vaccination of a conjugate vaccine can induce systemic as well as enhanced mucosal and memory B-cell anti-polysaccharide responses.

Chromobacterium violaceum is an emerging environmental pathogen that causes life-threatening infection in humans and animals. In October 2017, a Bangladeshi farmer was hospitalized with high-grade fever due to an agricultural injury–related wound infection. Bacteriological and 16S rRNA gene investigation detected C. violaceum in the wound discharge. The patient recovered successfully after a combination treatment with meropenem and ciprofloxacin, followed by prolonged medication to avoid recurrence. We strongly propose to incorporate C. violaceum in the differential diagnosis of wound and skin infections occurring in tropical and subtropical regions, especially when the injury was exposed to soil or sluggish water.

Diarrheal diseases remain a significant contributor to the global burden of disease. Climate change may increase their incidence by altering the epidemiology of waterborne pathogens through changes in rainfall patterns. To assess potential impacts of future changes in rainfall patterns, we analyzed 33,927 cases of diarrhea across all Ministry of Health clinical facilities in Esmeraldas Province, Ecuador, for a 24-month period from 2013 to 2014, using mixed-effects Poisson regression. We assessed the association between the incidence of diarrheal diseases and heavy rainfall events (HREs) and antecedent rainfall conditions. In rural areas, we found no significant associations between HREs and incidence. In urban areas, dry antecedent conditions were associated with higher incidence than wet conditions. In addition, HREs with dry antecedent conditions were associated with elevated incidence by up to 1.35 (incidence rate ratio, 95% CI: 1.14–1.60) times compared with similar conditions without HREs. These patterns may be driven by accumulation of fecal contamination during dry periods, followed by a flushing effect during HREs. This phenomenon is more important in dense urban environments with more impervious surfaces. These findings suggest that projected increases in rainfall variability and HREs may increase diarrhea burden in urban regions, which are rapidly expanding globally.

Identifying predictors of loss to follow-up (LTFU; treatment lapse ≥ 2 months) among people with tuberculosis (TB) may assist programmatic efforts in controlling the spread of TB. Newly diagnosed smear-positive TB patients were enrolled in the Regional Prospective Observational Research for TB study in Puducherry and Tamil Nadu, India. Treatment records were used to identify LTFU of those who were enrolled from May 2014 through December 2017. This nested case–control study evaluated male TB patients. Predictors were assessed using multivariable logistic regression. Of 425 men with TB, 82 (19%) were LTFU. In the adjusted analyses of males, divorced/separated marital status (adjusted odds ratio [aOR] 3.80; 95% CI: 1.39–10.38) and at-risk alcohol use (aOR 1.92; 95% CI: 1.12–3.27) were significant predictors for increased risk of LTFU, and diabetes was a significant predictor for decreased risk of LTFU (aOR 0.52; 95% CI: 0.29–0.92). Of 53 men with recorded date of last treatment visit, 23 (43%) and 43 (81%) had LTFU within the first 2 and first 4 months of treatment, respectively. Addressing at-risk alcohol use and providing more intensive follow-up could lead to improved treatment completion.

Costs related to tuberculosis (TB) can impose a significant burden on patients and their families and create barriers to diagnosis and treatment. Our study aimed to quantify out-of-pocket costs expended by TB patients in Bandung, Indonesia. This cross-sectional study recruited adults with TB from community health centers (CHCs), public and private hospitals, and private practitioners (PPs). An interview was completed at the time of diagnosis or at their return for 2- or 6-month treatment. Costs were converted to U.S. dollars (US$)—presented as median and interquartile range (IQR). Of 469 TB patients recruited, the mean age was 38 years and 57% were male. The median pretreatment direct cost per person was $37.51 (IQR 20.79–71.24). Hospitalization, diagnostic tests, and travel costs were predominant. Higher pretreatment costs were associated with no health insurance ($41.88 versus $27.41, P < 0.001), ≥ 6 visits to a healthcare provider ($39.91 versus $24.32, P < 0.001), ≥ 60 days pretreatment ($36.35 versus $26.25, P = 0.02), and presenting first to a PP ($40.71) or informal provider ($32.72) compared with private hospital ($21.26), public hospital ($19.63), or CHC ($13.52) (P = 0.01). For a subsample of 106 patients with total pre- and posttreatment costs available, the median total cost was $243.66 (IQR 128.46–550.71). For 26.5% of these patients, total costs were ≥ 20% of their annual household income. Despite having a good network of free TB diagnostic and treatment services throughout Bandung, patients experienced significant out-of-pocket costs. Increased uptake of the National Health Insurance, and systems for early recognition and diagnosis of TB, will contribute toward reducing costs.

GeneXpert® Edge (GX-Edge) is a new point-of-care platform not yet tested in the field. In this proof-of-concept study conducted for the diagnosis of tuberculosis in communities living alongside two large rivers of the Brazilian Amazon, we demonstrate that GX-Edge implemented in boats to offer onsite testing is a feasible strategy to investigate potentially devastating diseases such as tuberculosis in difficult-to-reach populations, such as riverside communities.

Stigma is an important social determinant of health-seeking behavior; however, the nature and extent of its association with depression among people living with multidrug-resistant tuberculosis (MDR-TB) are not well-understood. We enrolled 200 microbiologically confirmed MDR-TB inpatients at a TB specialist hospital in KwaZulu-Natal Province, an area considered the epicenter for MDR-TB coinfection in South Africa. Four aspects of stigma and their association with major depression were assessed through individual interviews: 1) community and 2) patient perspectives toward TB, and 3) community and 4) patient perspectives toward HIV. A major depressive episode (MDE), HIV coinfection, and low income were significantly associated with greater stigma subscales. Based on an adjusted regression model, the MDE was the only factor independently associated with (all aspects of) stigma. These results indicate the potential utility of addressing stigma associated with the MDE as an important step in improving health-seeking behavior to promote adherence and retention in care.

MPT64 is a 24-kDa immunogenic protein that is widely used as a diagnostic marker for the differentiation of Mycobacterium tuberculosis complex (MTBC) from nontuberculous Mycobacterium (NTM). Unlike Mycobacterium bovis, Bacillus Calmette-Guerin (BCG) vaccine strains with RD2 deletion do not secrete MPT64. Culture isolates from infections due to these strains may be falsely identified as nontuberculous Mycobacterium in the absence of clinical correlation. Here, we present one case each of BCG adenitis and osteitis, both of which were considered as MPT64 card–negative Mycobacterium spp. (i.e., NTM) and were later identified as M. bovis BCG Danish 1331 strain. The first case was a 4-month-old female infant admitted with swollen lymph nodes in the left supraclavicular and the left axillary region of 1 month duration. The second case was of a 1-year-and-5-month-old male child who presented with a limp on the left leg and soft tissue swelling of 1 month duration on the anterolateral aspect of the left knee joint. In both cases, BCG vaccine was administered at birth on the left deltoid region and had healed without any complication. Clinical samples in both cases were positive by Xpert tuberculosis/RIF for MTBC, and cultures grew acid-fast bacilli which were negative by MPT64 assay. The clinical implication of infections due to M. bovis BCG is immense as they are inherently resistant to pyrazinamide, and the presence of disseminated BCG infection in young children is a hallmark of serious immune deficiency which needs to be ruled out.

Diffuse cutaneous leishmaniasis (DCL) is a rare type of leishmaniasis characterized by diffuse skin lesions. In Brazil, Leishmania (L.) amazonensis is the main etiological agent of this clinical form. The state of Maranhão has the highest prevalence of this disease in the country, as well as a high rate of HIV infection. Here, we report the first case of DCL/HIV of Brazil. A 46-year-old man from the Amazonian area of Maranhão state presented atypical lesion in the left upper limb and dissemination of diffuse erythematous nodules over his entire body. Histopathological examination confirmed the presence of intracellular amastigotes of Leishmania, and a polymerase chain reaction and molecular identification by restriction fragment profile identified L. (L.) amazonensis as the causative agent of the disease. The patient was also diagnosed with HIV virus after the leishmaniasis diagnosis. The initial treatments for leishmaniasis were liposomal amphotericin B (AmB-L) (4 mg/kg) for 10 days and prophylactic use of Glucantime® (10 mg/Sb+5/kg) for 2 months. After unsuccessful initial treatments, he was treated with a combination of AmB-L (4 mg/kg) alternated with pentamidine (4 mg/kg) for 10 days but failed in the first therapeutic cycle. Subsequently, he had a good response to treatment with pentamidine (4 mg/kg).

We present two cases of Leishmania (V) panamensis in returning travelers from Central America successfully treated with miltefosine. The couple presented with ulcerative skin lesions nonresponsive to antibiotics. Skin biopsy with polymerase chain reaction (PCR) revealed L. (V) panamensis. To prevent the development of mucosal disease and avoid the inconvenience of parental therapy, we treated both patients with oral miltefosine. We suggest that miltefosine represents an important therapeutic alternative in the treatment of cutaneous lesions caused by L. panamensis and in preventing mucosal involvement.

In clinical practice, mixed-species malaria infections are often not detected by light microscopy (LM) or rapid diagnostic test, as a low number of parasites of one species may occur. Here, we report the case of an 8-year-old girl migrating with her family from Afghanistan with a two-species mixed infection with Plasmodium vivax and Plasmodium ovale. This case demonstrates the significance of molecular testing in the detection of mixed-species malaria infections and highlights the importance of a detailed data analysis during the medical validation procedure to prevent underestimation of mixed-species infections. To our knowledge, this is the first case report of a two-species mixed infection comprising both P. vivax and P. ovale confirmed by LM and different real-time polymerase chain reaction (PCR) approaches.

Four single-arm, prospective, clinical studies of pyronaridine–artesunate efficacy in uncomplicated Plasmodium falciparum or Plasmodium vivax malaria were conducted in Myanmar between 2017 and 2019. Eligible subjects were aged at least 6 years, with microscopically confirmed P. falciparum (n = 196) or P. vivax mono-infection (n = 206). Patients received pyronaridine–artesunate once daily for 3 days with follow-up until day 42 for P. falciparum or day 28 for P. vivax. For the primary efficacy analysis, adequate clinical and parasitological response (ACPR) in the per-protocol population at day 42 for P. falciparum malaria was 100% (88/88; 95% CI: 95.9, 100) in northern Myanmar (Kachin State and northern Shan State), and 100% (101/101; 95% CI: 96.4, 100) in southern Myanmar (Tanintharyi Region and Kayin State). Plasmodium falciparum day-3 parasite clearance was observed for 96.9% (190/196) of patients. Mutations in the P. falciparum Kelch propeller domain (K13) were detected in 39.0% (69/177) of isolates: F446I (14.7% [26/177]), R561H (13.0% [23/177]), C580Y (10.2% [18/177]), and P574L (1.1% [2/177]). For P. vivax, the day-28 ACPR was 100% (104/104; 95% CI: 96.5, 100) in northern Myanmar and 100% (97/97; 95% CI: 96.3, 100) in southern Myanmar. Across both P. vivax studies, 100% (206/206) of patients had day-3 parasite clearance. There were no adverse events. Pyronaridine–artesunate had excellent efficacy in Myanmar against P. falciparum and P. vivax and was well tolerated. This study supports the inclusion of pyronaridine–artesunate in national malaria treatment guidelines for Myanmar.

Plasmodium vivax and Plasmodium ovale form dormant liver hypnozoites that can reactivate weeks to months following initial infection. Malaria recurrences caused by relapses are an important cause of morbidity and source of transmission. To estimate the proportions of P. vivax malaria recurrences caused by relapses in different geographical locations, we systematically reviewed clinical efficacy studies of uncomplicated P. vivax malaria, in which patients were randomized to treatment with or without radical cure primaquine regimens and were followed up for 1 year. The minimum proportion of recurrences caused by relapses was estimated for each study site by assuming primaquine prevented all relapses and did not augment blood-stage efficacy. Of the 261 studies identified, six were eligible enrolling 4,092 patients from 14 treatment arm comparisons across seven countries. Of the 2,735 patients treated with primaquine, 24.3% received low dose (2.5 to < 5.0 mg/kg total) and 75.7% received high-dose primaquine (≥ 5.0 mg/kg total). The overall pooled incidence rate ratio of P. vivax relapses for patients treated with primaquine versus no primaquine was 0.15 (95% CI: 0.10–0.21; I 2 = 83.3%), equating to a minimum of 79% of recurrences attributable to relapse. Country-specific incidence rate ratios ranged from 0.05 (95% CI: 0.01–0.34; one estimate) in Pakistan to 0.34 in Nepal (95% CI: 0.12–0.83; one estimate) and Afghanistan (95% CI: 0.22–0.51; three estimates). Relapses account for a very high proportion of recurrent infections following schizontocidal treatment of acute P. vivax malaria across diverse geographic locations. This emphasizes the importance of implementing hypnozoitocidal treatment.

The emergence and spread of resistance in Plasmodium falciparum to the frontline treatment artemisinin-based combination therapies in Southeast Asia require close monitoring of the situation. Here, we collected 36 clinical samples of P. falciparum from the China–Myanmar border in 2014–2016, adapted these parasites to continuous culture, and performed in vitro drug assays on seven antimalarial drugs. Data for 23 parasites collected in 2010 and 2012 from the same area reported in an early study were used to assess longitudinal changes in drug sensitivity. Parasites remained highly resistant to chloroquine (CQ) and pyrimethamine, whereas they were generally sensitive to mefloquine (MFQ), lumefantrine (LMF), naphthoquine (NQ), and pyronaridine (PND). Parasites showed a similar temporal trend in sensitivity to CQ, NQ, and PND, with gradual reduction in the half-maximal inhibitory concentrations (IC50s) after 2012. The IC50s to the aminoalcohol drugs MFQ, LMF, and quinine (QN) all significantly declined in 2014, followed by various degrees of increase in 2016. Pyrimethamine displayed a continuous increase in IC50 over the years. The Dd2-like P. falciparum chloroquine-resistant transporter mutations were fixed or nearly fixed in the parasite population. The P. falciparum multidrug resistance 1 F1226Y mutation was detected in 80% parasites in 2016 and associated with reduced sensitivity to LMF and QN (P < 0.05). The N51I in P. falciparum dihydrofolate reductase and K540E/N and A581G in P. falciparum dihydropteroate synthase that are associated with antifolate resistance were either fixed or were approaching fixation in recent years. This study provides an updated picture and temporal trend of antimalarial drug resistance in the China–Myanmar border region, which will serve as a reference for antimalarial treatment.

Asymptomatic and/or low-density malaria infection has been acknowledged as an obstacle to achieving a malaria-free country. This study aimed to determine the prevalence of asymptomatic and/or low-density malaria infection in previously reported malarious localities using nested PCR in four states, namely, Johor, Pahang, Kelantan, and Selangor, between June 2019 and January 2020. Blood samples (n = 585) were collected and were extracted using a QIAamp blood kit. The DNA was concentrated and subjected to nested PCR. Thin and thick blood smears were examined as well. Of the 585 samples collected, 19 were positive: 10 for Plasmodium knowlesi, eight for Plasmodium vivax, and one for Plasmodium ovale. Asymptomatic and/or low-density malaria infection is a threat to malaria elimination initiatives. Eliminating countries should develop guidance policy on the importance of low-density malaria infection which includes detection and treatment policy.

Schistosomiasis is a serious public health issue in the world infecting more than 200 million people. In Maranhão state, Brazil, the disease has a high prevalence in the Baixada Maranhense microregion, where the socioeconomic conditions, high prevalence of freshwater snails, elevated incidence of human infection, and large rodent populations make the area highly conducive to the life cycle and persistence of schistosomiasis. The objective of this study was to record the perception of residents and health/public education professionals regarding this parasitosis and also understand their knowledge of the relationship between schistosomiasis and the environment. We conducted 53 interviews addressing the socioeconomic, behavioral, and environmental issues surrounding schistosomiasis. It was recorded that the population believed the environment is the main cause of the disease and the fisherman may be stigmatized by their chance of having the disease. Health/public educational professionals in the region indicated that there were no regular educational campaigns, which contributed to the high rates of reinfection and the difficulties in preventing and controlling the spread of the disease. These data clearly demonstrate the need for interdisciplinary work that engages the community in gathering and disseminating knowledge and developing solutions to minimize the occurrence of this major health issue in the region.

Liver fluke infection caused by Opisthorchis viverrini is recognized as a potential risk factor for cholangiocarcinoma (CCA). The National Strategic Plan to Control Liver Fluke Infection and Cholangiocarcinoma has implemented microscopic-based stool examination screening. However, eggs of O. viverrini and minute intestinal flukes (MIFs) are nearly morphologically similar and could result in inaccurate O. viverrini diagnosis. Stool specimens were collected from eight districts of Chiang Mai Province in northern Thailand. Opisthorchis-like eggs were identified with the Kato–Katz technique and differentiated for O. viverrini and MIFs using molecular study by PCR and PCR–restriction fragment length polymorphism targeting the internal transcribed spacer 2 (ITS2) gene. Prevalence of Opisthorchis-like eggs was 5.9% from a total of 9,570 specimens. From PCR assays, all liver flukes were O. viverrini and all MIFs were Haplorchis taichui. The distribution of species was H. taichui (38.2%), O. viverrini (10.5%), coinfection of H. taichui and O. viverrini (37.2%), and 14.1% were negative from PCR. Totally, H. taichui was found in 75.4% of infections from Opisthorchis-like specimens. ITS2 nucleotide sequencing analysis showed a single variant of O. viverrini with no variation and two variants of H. taichui. This study first revealed the genetic background of Opisthorchis-like eggs in northern Thailand. Minute intestinal flukes are occasionally misdiagnosed as O. viverrini leading to misinterpretation and overestimation of the burden of O. viverrini infection. Molecular diagnosis such as PCR could effectively discriminate species of Opisthorchis-like eggs and help shape the robustness of epidemiological data to control liver fluke infection and raise awareness of other risk factors for CCA.

Subarachnoid neurocysticercosis (SANCC) is a severe and progressive brain infection with Taenia solium. We performed a pilot study of noninvasive screening for SANCC in two endemic villages in northern Peru using a urine antigen screen followed by brain magnetic resonance imaging for participants with elevated levels of antigen. Among the 978 participants screened, we identified eight individuals with SANCC, many of whom were asymptomatic. This represents a minimum prevalence of 0.8% of SANCC, a level higher than expected based on prior studies, and a positive predictive value of 62% for our novel urine screening test. Future studies should confirm whether early detection and management improve clinical outcomes.

Gnathostomiasis is a helminthic infection caused by the third-stage larvae of nematodes of the genus Gnathostoma. The life cycle in humans starts with an enteric phase, with the worm perforating the gastric or intestinal mucosa to reach the peritoneal cavity and migrating through the human body. Subsequent penetration through the diaphragm may produce pleuropulmonary symptoms. We herein present a previously healthy 56-year-old Thai man from Southern Thailand who was an ex-smoker presented with chronic dry cough progressing to hemoptysis after consuming grilled swamp eels and freshwater fish. Chest computed tomography showed consolidation at the lingular segment, and the differential diagnosis was primary lung cancer and pulmonary tuberculosis. The lung tissue biopsied during bronchoscopy displayed segments of organisms with the phenotypic characteristics of Gnathostoma spp., and abundant eosinophils were seen in the alveolar tissue. Gnathostoma spinigerum infection was confirmed by a Western blot assay for G. spinigerum–specific 24-kDa reactive band. The patient received albendazole, and a follow-up chest radiograph revealed improvement in the consolidation in the lung and reduction in hemoptysis. We report the first direct evidence including pathology and immunohistochemistry of Gnathostoma invasion via the human lung, with clinical and radiographic presentations mimicking either malignancy or chronic infection.

Wambabya–Rwamarongo onchocerciasis focus is one of the eight foci Uganda verified using the WHO verification guidelines. The approach for elimination was twice yearly treatment with ivermectin for every round, treating at least 90% of all the eligible population. This was in combination with vector elimination using Abate® (BASF SE, Limburgerhof, Germany) since elimination nationwide policy was launched. From 2008 to 2013, the program distributed ivermectin with a mean treatment coverage of the ultimate treatment goal (UTG) or eligible population of 91.2%, with a range of 85–96%. In 2009, vector elimination based on ground larviciding had a dramatic impact on the Simulium vectors, as the last fly was observed in October 2009. No more Simulium vectors were observed during a period of at least 7 years, including the 3-year posttreatment surveillance (PTS) until the focus was reclassified as eliminated in August 2017. During the PTS period, none of the 10,578 trapped crabs were found infested with the aquatic stages of the vector. The last infested crab was observed in March 2010, and for at least 7 years, no infested crabs were observed. Serological surveys showed that of 2,978 young children examined in 2013, only one was OV16 positive (0.0%; 95% CI: 0–0.21). In 2017, after the PTS period, all 3,079 young children examined were negative for OV16 (95% CI: 0–0.16). Therefore, entomological and serological results provided evidence that resulted in the reclassification of Wambabya–Rwamarongo focus from “transmission interrupted” to “transmission eliminated” with no possibility of recrudescence.

Public spaces are common sites of fecal contamination which is concerning considering the prevalence rates of gastrointestinal pathogens carried by pets. Multiple pet-bound parasite species capable of infecting humans have previously been reported in fecal samples collected from urban areas around the globe, including Italy. In addition, the presence of gastrointestinal parasites has recently been shown in pets from the island of Sardinia, a well-known touristic destination. For these reasons, this study aims to evaluate the level of fecal contamination of two of the most important cities on Sardinia. Furthermore, the presence of endoparasites in fecal samples collected was also investigated to assess the parasitological risks associated with such contamination. A grid approach using a geographical information system was applied, followed by transect counting and sampling. A total of 956 and 220 dog feces with an average feces count of 4.7 and 2.6 per 100 linear meters were found for Sassari and Alghero, respectively. In Sassari 15.6% (52/333) and in Alghero 6.8% (6/88) of the samples tested positive for parasitic elements. Hookworms, Strongyloides stercoralis, Toxocara sp., and Trichuris vulpis were among the parasites most identified. This study showed significant urban contamination of both Sassari and Alghero with dog feces and the parasites within them, including potentially zoonotic species. The general public as well as tourists visiting the island should be aware of the risks associated with this and appropriate measures taken.

Some recent studies suggest ongoing transmission of parasitic diseases in the American South; however, surveys in Mississippi children are lacking. We enrolled 166 children (median age 8 years, range 4–13 years) from the Mississippi Delta region and carried out multi-parallel real-time polymerase chain reaction (PCR) for Necator americanus, Ascaris lumbricoides, and Strongyloides stercoralis on their stool samples. Dried blood spots were obtained for multiplex serology antibody detection. Of 166 children, all reported having flushable toilets, 11% had soil exposure, and 34% had a pet dog or cat. None had prior diagnosis or treatment of parasitic disease. Multi-parallel real-time PCRs were negative on the 89 stool DNA extracts available for testing. Dried blood spot testing of all 166 children determined the seroprevalence of IgG antibodies to Toxocara spp. (3.6%), Cryptosporidium (2.4%), S. stercoralis, Fasciola hepatica, and Giardia duodenalis (all 0%). In conclusion, parasitic infections and exposure were scarce in this population. Larger studies of at-risk populations are needed.

A 32-year-old medical practitioner presented to the emergency department with complaints of severe abdominal pain, fever, and vomiting, 1 week after the diagnosis of COVID-19. The patient did not report any comorbid conditions, alcohol usage, or gallstone disease. Laboratory and radiological investigations revealed the diagnosis of acute pancreatitis. He underwent conservative management and was discharged after 3 days of hospital admission. This case highlights a possible association between COVID-19 and acute pancreatitis, and the need for clinicians to carefully evaluate patients presenting with gastrointestinal complaints during the current pandemic.

A 70-year-old Dominican Republic man presented with lower back pain for 10 days. Fifteen days before pain onset, he had low-grade fever, chills, and asthenia, and 4 days before admission, he had constipation, malaise, generalized weakness, anorexia, nausea, and vomiting. On admission, the patient was afebrile and hypotensive, with a heart rate of 105 and an oxyhemoglobin saturation on room air of 95%. Hyponatremia, lymphopenia, elevated C-reactive protein, and ferritin were observed in complementary tests. Computed tomography (CT) scan showed findings consistent with COVID-19 bilateral bronchopneumonia, and an increase in size and blurring (loss of the Y shape) of both adrenals indicative of acute bilateral adrenal hemorrhage. The patient tested negative by reverse transcription polymerase chain reaction (RT-PCR) of nasopharyngeal swab, yet positive for IgG and IgM by ELISA, suggesting COVID-19 diagnosis.

COVID-19 represents the greatest health challenge of modern years. The spectrum of illness comprises respiratory and non-respiratory manifestations. We report the case of an adult man with COVID-19 who presented with rhabdomyolysis as a principal extrapulmonary manifestation. Our patient presented with dyspnea, fever, and muscle pain. After a comprehensive approach, the diagnosis of COVID-19 and rhabdomyolysis was made. He developed acute kidney injury requiring renal replacement therapy without reversibility, despite optimal treatment. We performed a literature search for similar cases, discuss the potential mechanisms implied, and propose a diagnostic-therapeutic algorithm.

COVID-19 is a pandemic caused by SARS-CoV-2, primarily affecting the respiratory tract. Pulmonary complications of COVID-19 may include acute respiratory distress syndrome and pulmonary embolism. Pneumothorax has been recently reported in association with COVID-19. We report a case of COVID-19 pneumonia with bilateral spontaneous pneumothorax with no known underlying lung disease or risk factors.

COVID-19 is a recent outbreak in China and rapidly spread worldwide. Lung consolidation is the most common radiologic finding of COVID-19 pneumonia. Pneumothorax has been rarely reported as a complication of severe COVID-19 pneumonia. Early recognition and management are detrimental to the outcome. We here report three cases of SARS-CoV-2 infection complicated by pneumothorax. In addition, we present a brief literature review.

As the COVID-19 pandemic progresses, awareness of uncommon presentations of the disease increases. Such is the case with pneumothorax and pneumomediastinum. Recent evidence suggested that these can occur in the context of COVID-19 pneumonia, even in the absence of mechanical ventilation–related barotrauma. We present two patients with COVID-19 pneumonia complicated by pneumomediastinum. The first patient was a 55-year-old woman who developed COVID-19 pneumonia. Her clinical course was complicated by pneumothorax and pneumomediastinum, and, unfortunately, she died 2 days following the admission. The second patient was a 31-year-old man who developed a small pneumomediastinum and was managed conservatively. He had a spontaneous resolution of the pneumomediastinum and was discharged 19 days later. None of our patients required invasive or noninvasive positive pressure ventilation. We performed a literature review of COVID-19 pneumonia cases that developed pneumothorax, pneumomediastinum, or both. The analysis showed that the latter had high mortality (60%). Thus, it is necessary to pay attention to these complications as early identification and management can reduce the associated morbidity and mortality.

The COVID-19 pandemic represents a major public health, economic, political, and scientific concern in most countries around the globe where COVID-19 cases and deaths have been confirmed. This study assessed the attitudes, anxiety, and behavioral practices of university students in Jordan regarding COVID-19 during the early period of the infection (March 19–21, 2020) using a validated, self-administered survey questionnaire. Positive attitudes or low-risk practices were given 1 point, whereas negative attitudes or high-risk practices were scored 0. Percentages of the total score were used for categorizing data into negative attitudes or high-risk practices (≤ 60%), moderate attitudes or moderate-risk practices (60.01–80%), and positive attitudes or low-risk practices (> 80%). Generally, the university students displayed positive attitudes and low-risk practices toward preventing COVID-19, with an average score of 81.1% and 84.3%, respectively. Approximately two-thirds (69.1%) of the students showed a positive attitude toward COVID-19 seriousness, concern of contracting the virus, and the appropriate prevention measures, and low-risk practices (67.6%) toward preventing COVID-19 including implementation of social distancing and good hygiene. Female, older, medical, or postgraduate students practiced significantly more (P ≤ 0.05) appropriate hygiene and social distancing behaviors toward COVID-19 than their counterparts of each group. More than two-thirds (69.2%) of the students were anxious that they might become infected with COVID-19. These results are important for health authorities to develop appropriate educational programs and protective health measures including good respiratory etiquette and handwashing practices, to enhance safer lifestyles and prevent COVID-19 transmission.

Brazil is, at the time of writing, the global epicenter of COVID-19, but information on risk factors for hospitalization and mortality in the country is still limited. Demographic and clinical data of COVID-19 patients until June 11th, 2020 were retrieved from the State Health Secretariat of Espírito Santo, Brazil. Potential risk factors for COVID-19 hospitalization and death were analyzed by univariate and multivariable logistic regression models. A total of 10,713 COVID-19 patients were included in this study; 81.0% were younger than 60 years, 55.2% were female, 89.2% were not hospitalized, 32.9% had at least one comorbidity, and 7.7% died. The most common symptoms on admission were cough (67.7%) and fever (62.6%); 7.1% of the patients were asymptomatic. Cardiovascular diseases (23.7%) and diabetes (10.3%) were the two most common chronic diseases. Multivariate logistic regression analysis identified an association of all explanatory variables, except for cough and diarrhea, with hospitalization. Older age (odds ratio [OR] = 3.95, P < 0.001) and shortness of breath (OR = 3.55, P < 0.001) were associated with increase of odds to COVID-19 death in hospitalized patients. Our study provided evidence that older age, male gender, Asian, indigenous or unknown race, comorbidities (smoking, kidney disease, obesity, pulmonary disease, diabetes, and cardiovascular disease), as well as fever and shortness of breath increased the risk of hospitalization. For death outcome in hospitalized patients, only older age and shortness of breath increased the risk.

The COVID-19 pandemic and public health “lockdown” responses in sub-Saharan Africa, including Uganda, are now widely reported. Although the impact of COVID-19 on African populations has been relatively light, it is feared that redirecting focus and prioritization of health systems to fight COVID-19 may have an impact on access to non–COVID-19 diseases. We applied age-based COVID-19 mortality data from China to the population structures of Uganda and non-African countries with previously established outbreaks, comparing theoretical mortality and disability-adjusted life years (DALYs) lost. We then predicted the impact of possible scenarios of the COVID-19 public health response on morbidity and mortality for HIV/AIDS, malaria, and maternal health in Uganda. Based on population age structure alone, Uganda is predicted to have a relatively low COVID-19 burden compared with an equivalent transmission in comparison countries, with 12% of the mortality and 19% of the lost DALYs predicted for an equivalent transmission in Italy. By contrast, scenarios of the impact of the public health response on malaria and HIV/AIDS predict additional disease burdens outweighing that predicted from extensive SARS-CoV-2 transmission. Emerging disease data from Uganda suggest that such deterioration may already be occurring. The results predict a relatively low COVID-19 impact on Uganda associated with its young population, with a high risk of negative impact on non–COVID-19 disease burden from a prolonged lockdown response. This may reverse hard-won gains in addressing fundamental vulnerabilities in women and children’s health, and underlines the importance of tailoring COVID-19 responses according to population structure and local disease vulnerabilities.

Globally, healthcare systems are facing the enormous challenge of the COVID-19 pandemic. Ethiopia is currently implementing different preventive measures to interrupt the transmission of SARS-CoV-2. The early effect of these preventive measures on essential healthcare service delivery is unknown. In this study, we looked at the number of essential healthcare visits over 8 weeks, 4 weeks before and 4 weeks after the implementation of preventive measures. During the implementation of these measures, patient flow decreased in all elements of essential healthcare service. The decline was dramatic for family planning (98%), emergency surgery (77%), and follow-up of chronic surgical conditions (70%). An understanding of the reasons behind the decrease in patient flow is urgently needed to design ways of sustaining essential care.

The COVID-19 pandemic caught the world by surprise, causing millions of confirmed cases and hundreds of thousands of deaths. Hence, the Malaysian government announced a Movement Control Order at the start of the containment phase to flatten the epidemiological curve. Universiti Malaysia Sabah (UMS), a public university in Borneo, was accelerated into alert phase because of high risk of case importation from more than 400 China incoming undergraduates. Measures to mitigate the potential COVID-19 outbreaks in its population were taken by using conventional public health measures with special attention to task-shifting and widespread community mental health interventions. A Preparedness and Response Centre was established to overseer the mitigating measures happening inside the university. Measures taken included empowerment of frontline staff, strengthening of restrictions, strengthening university health center, vigorous contact tracing, widespread health education, maintaining cultural sensitivity, and establishment of early standard operating procedures and university continuity plans. Hence, UMS was able to ensure no importation of cases into its campus during both acute and containment phases at the nationwide level.

The quality and type of specimen collection affect the sensitivity of real-time reverse transcriptase–PCR (rRT-PCR) for the diagnosis of SARS-CoV-2. In this report, the course over time of rRT-PCR for SARS-CoV-2 in 26 clinical specimens collected from the upper (nasopharyngeal and throat swabs) and lower (sputum) respiratory tracts of COVID-19 cases with pneumonia was investigated along with the clinical course. The preliminary results revealed that higher SARS-CoV-2 RNA concentration and longer time for detection make self-collected sputum a preferable specimen for the diagnosis and follow-up of COVID-19 pneumonia. Self-collection of sputum can minimize the risk of unnecessary exposure to healthcare workers, preserve the shortage of personal protective equipment, and limit viral transmission to the environment.

The SARS-CoV-2 pandemic is now expanding into the developing world with devastating consequences. Departing from a population-based study in rural Ecuador where all adult individuals (aged 40 years or older) were tested for SARS-CoV-2 IgG and IgM antibodies, we expanded it to include a house-based case–control component assessing in-house clustering and other variables potentially associated with infection. We selected houses where exactly two study participants lived and were both seropositive (case-houses), and matched 1:1 to control-houses where both were seronegative. Younger household members had an antibody test performed. Infected household members were found in 33 (92%) case-houses and in only six (17%) control-houses. In 28/29 discordant house pairs, the case-house had seropositive household members and the control-house did not (odds ratio: 28; 95% CI: 4.6–1,144). Our data demonstrate strong in-house clustering of infection in community settings, stressing the importance of early case ascertainment and isolation for SARS-CoV-2 control.

COVID-19 is an emerging disease threatening the lives of patients and healthcare workers (HCWs) alike. In this article, we present initial results of COVID-19 screening performed among the hospital staff of an infectious diseases referral hospital in Manila, the Philippines. Of 324 HCWs tested, eight were positive; only one was exposed to COVID-19 patients, whereas seven others belonged to two different departments. Routine screening of hospital staff is invaluable for the safety of the HCWs and the patients in hospitals and should be performed on a regular basis. In monitoring HCWs, we protect one of our most valuable assets against COVID-19.

Murine models of SARS-CoV-2 infection are critical for elucidating the biological pathways underlying COVID-19. Because human angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV-2, mice expressing the human ACE2 gene have shown promise as a potential model for COVID-19. Five mice from the transgenic mouse strain K18-hACE2 were intranasally inoculated with SARS-CoV-2 Hong Kong/VM20001061/2020. Mice were followed twice daily for 5 days and scored for weight loss and clinical symptoms. Infected mice did not exhibit any signs of infection until day 4, when no other obvious clinical symptoms other than weight loss were observed. By day 5, all infected mice had lost around 10% of their original body weight but exhibited variable clinical symptoms. All infected mice showed high viral titers in the lungs as well as altered lung histology associated with proteinaceous debris in the alveolar space, interstitial inflammatory cell infiltration, and alveolar septal thickening. Overall, these results show that the K18-hACE2 transgenic background can be used to establish symptomatic SARS-CoV-2 infection and can be a useful mouse model for COVID-19.

Emergence of SARS-CoV-2 in dengue virus (DENV)–endemic areas complicates the diagnosis of both infections. COVID-19 cases may be misdiagnosed as dengue, particularly when relying on DENV IgM, which can remain positive months after infection. To estimate the extent of this problem, we evaluated sera from 42 confirmed COVID-19 patients for evidence of DENV infection. No cases of SARS-CoV-2 and DENV coinfection were identified. However, recent DENV infection, indicated by the presence of DENV IgM and/or high level of IgG antibodies, was found in seven patients. Dengue virus IgM and/or high IgG titer should not exclude COVID-19. SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) testing is appropriate when dengue nonstructural protein 1 (NS1) or RT-PCR is negative. Given the possibility of coinfection, testing for both DENV and SARS-CoV-2 is merited in the setting of the current pandemic.

Dengue-related mortality has significantly reduced with early and appropriate fluid resuscitation. However, we continue to see dengue-related fatalities in patients despite early intervention and advanced critical care support. This was a retrospective study conducted at a tertiary care private hospital in Mumbai, India. All patients dying of dengue in the calendar year 2017 were studied. Details related to age, gender, condition at presentation, laboratory parameters, treatment administered, and time to death were abstracted from case records. A total of 575 patients with a diagnosis of dengue were admitted to the hospital in 2017, of which 15 died (mortality rate 2.6%). Four patients died in the emergency medical unit; 11 patients who died after admission to the inpatient unit had multi-organ dysfunction at the time of presentation, with shock, severe liver dysfunction, and severe metabolic acidosis. Only 4/11 patients had hemoconcentration, and 10/11 patients had high white cell counts. In five patients where serum ferritin was performed, it was more than 40,000 ng/mL. Death occurred at a median time of 2 days after hospitalization despite good supportive care. Although there is scope for improvement of supportive care in these patients, it appears that other interventions are urgently needed to improve outcomes in severe dengue. This calls for more research into the immunopathology of dengue, evaluation of anti-inflammatory drugs, intravenous immunoglobulins, antivirals, and improved vaccines.

Zoonotic pathogens such as arboviruses have comprised a significant proportion of emerging infectious diseases in humans. The role of wildlife species as reservoirs for arboviruses is poorly understood, especially in endemic areas such as Southeast Asia. This study aims to determine the exposure history of different macaque species from national parks in Thailand to mosquito-borne flaviviruses and alphavirus by testing the serum samples collected from 25 northern pigtailed macaques, 33 stump-tailed macaques, and 4 long-tailed macaques for the presence of antibodies against dengue, Zika, and chikungunya viruses by plaque reduction neutralization assay. Specific neutralizing antibodies against Dengue virus (DENV1-4) and Zika virus (ZIKV) were mainly found in stump-tailed macaques, whereas neutralizing antibody titers were not detected in long-tailed macaques and pigtailed macaques as determined by 90% plaque reduction neutralization assay (PRNT90). One long-tailed macaque captured from the south of Thailand exhibited antibody titers against chikungunya virus (CHIKV), suggesting enzootic of this virus to nonhuman primates (NHPs) in Thailand. Encroachment of human settlements into the forest has increased the interface that exposes humans to zoonotic pathogens such as arboviruses found in monkeys. Nonhuman primates living in different regions of Thailand showed different patterns of arboviral infections. The presence of neutralizing antibodies among wild monkeys in Thailand strongly suggests the existence of sylvatic cycles for DENV, ZIKV, and CHIKV in Thailand. The transmission of dengue, Zika, and chikungunya viruses among wild macaques may have important public health implications.

Mosquito-borne flaviviruses are emerging pathogens of an increasing global public health concern because of their rapid increase in geographical range and the impact of climate change. Japanese encephalitis virus (JEV) and West Nile virus (WNV) are of concern because of the risk of reemergence and introduction by migratory birds. In Singapore, human WNV infection has never been reported and human JEV infection is rare. Four sentinel vector surveillance sites were established in Singapore to understand the potential risk posed by these viruses. Surveillance was carried out from August 2011 to December 2012 at Pulau Ubin, from March 2011 to March 2013 at an Avian Sanctuary (AS), from December 2010 from October 2012 at Murai Farmway, and from December 2010 to December 2013 at a nature reserve. The present study revealed active JEV transmission in Singapore through the detection of JEV genotype II in Culex tritaeniorhynchus collected from an Avian Sanctuary. Culex flavivirus (CxFV), similar to the Quang Binh virus isolated from Cx. tritaeniorhynchus in Vietnam and CxFV-LSFlaviV-A20-09 virus isolated in China, was also detected in Culex spp. (vishnui subgroup). No WNV was detected. This study demonstrates the important role that surveillance plays in public health and strongly suggests the circulation of JEV among wildlife in Singapore, despite the absence of reported human cases. A One Health approach involving surveillance, the collaboration between public health and wildlife managers, and control of mosquito populations remains the key measures in risk mitigation of JEV transmission in the enzootic cycle between birds and mosquitoes.

In any outbreak situation, a poor stakeholder response can impede the outbreak control and can have high economic and social cost. We conducted a qualitative study to understand stakeholder response in handling of the Nipah deceased persons during the outbreak of Nipah in Kerala, 2018. To understand the responses and to generate knowledge from the data, we used grounded theory approach for the study and conducted in-depth interviews and focus group discussion. Mixed public response and swift state response emerged as the main themes in our study. Under the “mixed public response,” three categories emerged, including anxiety and fear, conflicting religious beliefs, and humanitarian concern. Under the “swift state response,” the categories emerged were critical resources and robust guidance. A collective effort involving the administration, local and religious groups, and a culturally acceptable scientific protocol proved to be good examples of gaining social acceptance. Kerala puts forth a model of efficient community engagement and communication to gain public support and acceptance in a fatal disease outbreak.

Since its reintroduction in 2015, rabies has been established as an enzootic disease among the dog population of Arequipa, Peru. Given the unknown rate of dog bites, the risk of human rabies transmission is concerning. Our objective was to estimate the rate of dog bites in the city and to identify factors associated with seeking health care in a medical facility for wound care and rabies prevention follow-up. To this end, we conducted a door-to-door survey with 4,370 adults in 21 urban and 21 peri-urban communities. We then analyzed associations between seeking health care following dog bites and various socioeconomic factors, stratifying by urban and peri-urban localities. We found a high annual rate of dog bites in peri-urban communities (12.4%), which was 2.6 times higher than that in urban areas (4.8%). Among those who were bitten, the percentage of people who sought medical treatment was almost twice as high in urban areas (39.1%) as in peri-urban areas (21.4%).

Access to good-quality medicines remains a contentious issue in developing countries. This development is worrisome, particularly in a setting with a high incidence of malaria. Monitoring of antimalarial drugs in the commercial domain becomes necessary; thus, we evaluated the quality of artemether injection marketed in Southwest Nigeria. A cross-sectional survey was conducted to obtain 22 different brands of artemether injections within Southwest Nigeria. The samples were examined for their sources, lot numbers, containers for injection, oil base used for preparation, and dates of expiration. Further analysis involved visual inspection, assessment of extractable volume, identity tests, and an assay of active pharmaceutical ingredient. The pharmaceutical quality of each sample was determined according to the criteria set in the International Pharmacopoeia 2019. None of the products had any particulate matter, but there were certain irregularities in their presentation. Eighteen of the 22 products (81.7%) were packaged in plain instead of amber-colored ampoules, and 77.3% (17/22) did not indicate the oil base used as the vehicle on the label as against the pharmacopoeial standard. Sixteen products (72.7%) passed the extractable volume test, although the remaining 22.3% did not conform to the extractable volume per unit dose. Artemether was present in all the samples, although only 40.9% (9/22) met the recommended percentage content of 90–110% of artemether. The study revealed the presence of a high percentage of substandard artemether injection products marketed in Nigeria. Further surveillance is warranted to confirm the quality of artemether injection circulated in other regions within Nigeria.

Campylobacter has emerged as a potential important cause of childhood morbidity in sub-Saharan Africa. Biannual mass azithromycin distribution has previously been shown to reduce all-cause child mortality in sub-Saharan Africa. We conducted a randomized controlled trial in Burkina Faso in which children were randomized in a 1:1 fashion to a 5-day course of azithromycin or placebo to investigate the effect of oral antibiotics on the gut microbiome. We evaluated the changes in the gut microbiome of preschool children treated with azithromycin using metagenomic DNA sequencing. We found that three Campylobacter species were reduced with azithromycin treatment compared with placebo. These results were consistent with other studies that have shown decreases in Campylobacter species after azithromycin treatment, generating the hypothesis that a decrease in Campylobacter may contribute to observations of reduction in mortality following azithromycin distribution.

As one of the six consortia funded through the NIH Fogarty International Center, the University of North Carolina at Chapel Hill, Johns Hopkins University, Morehouse School of Medicine, and Tulane University (UJMT) Fogarty Global Health Fellows Program provides postdoctoral trainees and doctoral students support and training for yearlong research attachments at selected low- and middle-income countries. To understand the current impact of this global health research training opportunity, the UJMT consortium conducted a crowdsourcing contest to gather creative messages to promote and improve the impact of the program in partnership with Social Entrepreneurship to Spur Health. Between January and March 2019, the contest received a total of 47 submissions from 14 countries; 44 were found eligible. After judging, 19 (41.2%) submissions received a mean score of 7 or higher. We examined both textual and descriptive submissions for emergent themes and identified a range of facilitators who can be used to further improve the training programs; examples include exceptional mentorship, acquisition of research skills, career development, personal development, and multisite training opportunities. In conclusion, the crowdsourcing mentorship contest demonstrated the feasibility and acceptability of leveraging existing research networks for community engagement and how useful information can be effectively collected to highlight the effectiveness of a program and expand the reach.

Though bulk stool remains the gold standard specimen type for enteropathogen diagnosis, rectal swabs may offer comparable sensitivity with greater ease of collection for select pathogens. This study sought to evaluate the validity and reproducibility of rectal swabs as a sample collection method for the molecular diagnosis of Giardia duodenalis. Paired rectal swab and bulk stool samples were collected from 86 children ages 0–4 years living in southwest Niger, with duplicate samples collected among a subset of 50 children. Infection was detected using a previously validated real-time PCR diagnostic targeting the small subunit ribosomal RNA gene. Giardia duodenalis was detected in 65.5% (55/84) of bulk stool samples and 44.0% (37/84) of swab samples. The kappa evaluating test agreement was 0.81 (95% CI: 0.54–1.00) among duplicate stool samples (N = 49) and 0.75 (95% CI: 0.47–1.00) among duplicate rectal swabs (N = 48). Diagnostic sensitivity was 93% (95% CI: 84–98) by bulk stool and 63% (95% CI: 49–75) by rectal swabs. When restricting to the lowest three quartiles of bulk stool quantitation cycle values (an indication of relatively high parasite load), sensitivity by rectal swabs increased to 78.0% (95% CI: 64–89, P < 0.0001). These findings suggest that rectal swabs provide less sensitive and reproducible results than bulk stool for the real-time PCR diagnosis of G. duodenalis. However, their fair sensitivity for higher parasite loads suggests that swabs may be a useful tool for detecting higher burden infections when stool collection is excessively expensive or logistically challenging.

The recent Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial reported a reduction in child mortality following biannual azithromycin mass drug administration (MDA). Here, we investigate the financial costs and cost-effectiveness from the health provider perspective of azithromycin MDA at the MORDOR-Malawi study site. During MORDOR, a cluster-randomized trial involving biannual azithromycin MDA or placebo to children aged 1–59 months, fieldwork-related costs were collected, including personnel, transport, consumables, overheads, training, and supervision. Mortality rates in azithromycin- and placebo-treated clusters were calculated overall and for the five health zones of Mangochi district. These were used to estimate the number needed to treat to avert one death and the costs per death and disability-adjusted life year (DALY) averted. The cost per dose of MDA was $0.74 overall, varying between $0.63 and $0.94 in the five zones. Overall, the number needed to treat to avert one death was 1,213 children; the cost per death averted was $898.47, and the cost per DALY averted was $9.98. In the three zones where mortality was lower in azithromycin-treated clusters, the number needed to treat to avert one death, cost per death averted, and cost per DALY averted, respectively, were as follows: 3,070, $2,899.24, and $32.31 in Monkey Bay zone; 1,530, $1,214.42, and $13.49 in Chilipa zone; and 344, $217.98, and $2.42 in Namwera zone. This study is a preliminary cost-effectiveness analysis that indicates azithromycin MDA for reducing child mortality has the potential to be highly cost-effective in some settings in Malawi, but the reasons for geographical variation in effectiveness require further investigation.

Mass azithromycin distribution has been shown to reduce all-cause mortality in preschool children in sub-Saharan Africa. However, substantial heterogeneity in the apparent effect has been noted across geographic settings, suggesting a greater relative benefit in higher mortality settings. Here, we evaluated the relationship between the underlying mortality rate and the efficacy of azithromycin for the prevention of child mortality using data from multiple sites in Ethiopia, Malawi, Niger, and Tanzania. Between regions, we find no strong evidence of effect modification of the efficacy of azithromycin distribution for the prevention of child mortality by the underlying mortality rate (P = 0.12), although a modest effect is consistent with our findings. Higher mortality settings could be prioritized, however, because of the larger number of deaths which could be averted with azithromycin distribution.

We examined whether baseline mortality risk, as a function of child age and site, modified the azithromycin mortality-reduction effect in the Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) clinical trial. We used the Cox proportional hazards model with an interaction term. Three models were examined representing three sources for the baseline-risk covariate: two using sources external to MORDOR and the third leveraging data within MORDOR. All three models provided moderate evidence for the effect becoming stronger with increasing baseline mortality (P = 0.02, 0.02, and 0.07, respectively) at the rate of approximately 6–12% additional mortality reduction per doubling of baseline mortality. Etiological and programmatic implications of these findings are discussed.

The Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance study showed that administration of biannual, single-dose azithromycin to preschool children reduces mortality. We sought to evaluate its impact on azithromycin resistance. Thirty randomly selected communities in Kilosa district, Tanzania, were randomized to receive 6-monthly single-dose azithromycin (∼20 mg/kg) versus placebo treatment of children aged 1–59 months. From each community, 40 children (aged 1–59 months) were randomly selected at baseline, 12 and 24 months. Isolation and resistance testing of Streptococcus pneumoniae and Escherichia coli were evaluated using nasopharyngeal and rectal swabs, respectively. The carriage prevalence and the proportion of azithromycin-resistant isolates were determined using disk diffusion. At baseline, the characteristics of the randomly selected children were similar by treatment arms. Both at baseline and in annual cross-sectional surveys, rates of S. pneumoniae and E. coli isolation between treatment arms were similar. The proportions of azithromycin-resistant S. pneumoniae isolates in the children in communities treated with azithromycin versus placebo at baseline, 12 months, and 24 months were 26.5% (18.1%; P = 0.26), 26.8% (16.5%; P = 0.29), and 13.4% (17.0%; P = 0.57), respectively. The proportions of azithromycin-resistant E. coli isolates at baseline, 12 months, and 24 months in the azithromycin (versus placebo) arms were 14.9% (18.9%; P = 0.16), 21.5% (16.6%; P = 0.10), and 14.9% (14.7%; P = 0.95), respectively. Over the 24 months, the mean treatment coverage for the azithromycin and placebo was 76.9% and 74.8%, respectively (P = 0.49). Biannual administration of single-dose azithromycin to children did not appear to result in excess azithromycin resistance in S. pneumoniae and E. coli isolates over 24 months of follow-up.

Biannual mass azithromycin distribution to children younger than 5 years has been shown to reduce all-cause mortality in sub-Saharan Africa. Antibiotic-sparing approaches to azithromycin distribution, such as targeting to younger children who are at higher risk of mortality, are being considered by policymakers. We evaluated the absolute number of deaths averted in the Macrolides Oraux pour Réduire le Décès avec un Oeil sur la Résistance study in three age-groups: 1–5 months, 1–11 months, and 1–59 months. The number of deaths averted decreased from 729 (95% CI 492 to 966) in children aged 1–59 months to 297 (95% CI 168 to 427) and 126 (95% CI 43 to 209) in the 1- to 11-month and 1- to 5-month groups, respectively. Limiting antibiotic treatment to a subgroup of higher risk children may result in fewer deaths averted compared with treating all preschool children.

A cluster-randomized clinical trial showed that biannual single-dose azithromycin reduced mortality in preschool children; we sought to determine the effect on anemia. A simple random sample of 30 communities from Kilosa district, Tanzania, were themselves randomized to receive either 6-monthly treatment of children aged 1–59 months with single-dose azithromycin or placebo. From each community, 40 preschool children were randomly selected at baseline, 12 months, and 24 months. At surveys, the children underwent hemoglobin testing; WHO definitions for anemia were applied. After adjusting for community clustering, the prevalence of anemia was not significantly different by treatment assignment at baseline, 12 months, and 24 months. In each of the cross-sectional surveys, anemia prevalence was associated with younger age; the odds of being anemic was highest in those aged < 12 months. There was also a general decrease in the prevalence of anemia during the study. Although azithromycin was not shown to affect anemia, significantly, the study highlights burden of anemia in rural, African communities.

The relationship between malaria and malnutrition is complicated, and existence of one may predispose or exacerbate the other. We evaluated the relationship between malaria parasitemia and nutritional status in children living in communities participating in a cluster-randomized trial of biannual azithromycin compared with placebo for prevention of childhood mortality. Data were collected during the low malaria transmission and low food insecurity season. Parasitemia was not associated with weight-for-height Z-score (24 months: P = 0.11 azithromycin communities, P = 0.75 placebo communities), weight-for-age Z-score (24 months: P = 0.83 azithromycin, P = 0.78 placebo), height-for-age Z-score (24 months: P = 0.30 azithromycin, P = 0.87 placebo), or mid-upper arm circumference (24 months: P = 0.12 azithromycin, P = 0.56 placebo). There was no statistically significant evidence of a difference in the relationship in communities receiving azithromycin or placebo. During the low transmission season, there was no evidence that malaria parasitemia and impaired nutritional status co-occur in children.

Recent evidence indicates mass drug administration with azithromycin may reduce child mortality. This study uses verbal autopsy (VA) to investigate the causes of individual deaths during the Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial in Malawi. Cluster randomization was performed as part of MORDOR. Biannual household visits were conducted to distribute azithromycin or placebo to children aged 1–59 months and update the census to identify deaths for VA. MORDOR was not powered to investigate mortality effects at individual sites, but the available evidence is presented here for hypothesis generation regarding the mechanism through which azithromycin may reduce child mortality. Automated VA analysis was performed to infer the likely cause of death using two major analysis programs, InterVA and SmartVA. A total of 334 communities were randomized to azithromycin or placebo, with more than 130,000 person-years of follow-up. During the study, there were 1,184 deaths, of which 1,131 were followed up with VA. Mortality was 9% lower in azithromycin-treated communities than in placebo communities (rate ratio 0.91 [95% CI: 0.79–1.05]; P = 0.20). The intention-to-treat analysis by cause using InterVA suggested fewer HIV/AIDS deaths in azithromycin-treated communities (rate ratio 0.70 [95% CI: 0.50–0.97]; P = 0.03) and fewer pneumonia deaths (rate ratio 0.82 [95% CI: 0.60–1.12]; P = 0.22). The use of the SmartVA algorithm suggested fewer diarrhea deaths (rate ratio 0.71 [95% CI: 0.51–1.00]; P = 0.05) and fewer pneumonia deaths (rate ratio 0.58 [95% CI: 0.33–1.00]; P = 0.05). Although this study is not able to provide strong evidence, the data suggest that the mortality reduction during MORDOR in Malawi may have been due to effects on pneumonia and diarrhea or HIV/AIDS mortality.

Reductions in malaria morbidity have been reported following azithromycin mass drug administration (MDA) for trachoma. The recent Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance (MORDOR) trial reported a reduction in child mortality following biannual azithromycin MDA. Here, we investigate the effects of azithromycin MDA on malaria at the MORDOR-Malawi study site. A cluster-randomized double-blind placebo-controlled trial, with 15 clusters per arm, was conducted. House-to-house census was updated biannually, and azithromycin or placebo syrup was distributed to children aged 1–59 months for a total of four biannual distributions. At baseline, 12-month, and 24-month follow-up visits, a random sample of 1,200 children was assessed for malaria with thick and thin blood smears and hemoglobin measurement. In the community-level analysis, there was no difference in the prevalence of parasitemia (1.0% lower in azithromycin-treated communities; 95% CI: −8.2 to 6.1), gametocytemia (0.7% lower in azithromycin-treated communities; 95% CI: −2.8 to 1.5), or anemia (1.7% lower in azithromycin-treated communities; 95% CI: −8.1 to 4.6) between placebo and azithromycin communities. Further interrogation of the data at the individual level, both per-protocol (including only those who received treatment 6 months previously) and by intention-to-treat, did not identify differences in parasitemia between treatment arms. In contrast to several previous reports, this study did not show an effect of azithromycin MDA on malaria parasitemia at the community or individual levels.