The American Journal of Tropical Medicine and Hygiene - Online First

Human African trypanosomiasis (HAT) remains a serious public health problem with diagnostic and treatment challenges in many African countries. The absence of a gold-standard biomarker has been a major difficulty for accurate disease staging and treatment follow-up. We therefore attempted to develop a simple, affordable, and noninvasive biomarker for HAT diagnosis and staging. Simultaneous actigraphy and polysomnography as well as CSF white blood cell (WBC) count, trypanosome presence, and CXCL-10 cytokine levels were performed in 20 HAT patients and nine healthy individuals (controls) using standard procedures. The International HIV Dementia Scale (IHDS) was scored in some patients as a surrogate for clinical assessment. From actigraphic parameters, we developed a novel sleep score and used it to determine correlations with other HAT markers, and compared their performance in differentiating between patients and controls and between HAT stages. The novel actigraphy sleep score (ASS) had the following ranges: 0–25 (healthy controls), 67–103 (HAT stage I), 111–126 (HAT intermediate), and 133–250 (HAT stage II). Compared with controls, stage I patients displayed a 7-fold increase in the ASS (P < 0.01), intermediate stage patients a 10-fold increase (P < 0.001), and HAT stage II patients an almost 20-fold increase (P < 0.001). CXCL-10 showed high interindividual differences. White blood cell counts were only marked in HAT stage II patients with a high interindividual variability. The International HIV Dementia Scale score negatively correlated with the ASS. We report the development and better performance of a new biomarker, ASS, for HAT diagnosis, disease staging, and monitoring that needs to be confirmed in large cohort studies.

Artemether–lumefantrine (AL) is a first-line agent for uncomplicated malaria caused by Plasmodium falciparum. The WHO recommends periodic therapeutic efficacy studies of antimalarial drugs for the detection of malaria parasite drug resistance and to inform national malaria treatment policies. We conducted a therapeutic efficacy study of AL in a high malaria transmission region of northern Zambia from December 2014 to July 2015. One hundred children aged between 6 and 59 months presenting to a rural health clinic with uncomplicated falciparum malaria were admitted for treatment with AL (standard six-dose regimen) and followed weekly for 5 weeks. Parasite counts were taken every 6 hours during treatment to assess parasite clearance. Recurrent episodes during follow-up (n = 14) were genotyped to distinguish recrudescence from reinfection and to identify drug resistance single nucleotide polymorphisms (SNPs) and mdr1 copy number variation. Day 7 lumefantrine concentrations were measured for correspondence with posttreatment reinfection. All children who completed the parasite clearance portion of the study (n = 94) were microscopy-negative by 72 hours. The median parasite elimination half-life was 2.7 hours (interquartile range: 2.1–3.3). Genotype-corrected therapeutic efficacy was 98.8% (95% CI: 97.6–100). Purported artemisinin and lumefantrine drug resistance SNPs in atp6, 3D7_1451200, and mdr1 were detected but did not correlate with parasite recurrence, nor did day 7 lumefantrine concentrations. In summary, AL was highly effective for the treatment of uncomplicated falciparum malaria in northern Zambia during the study period. The high incidence of recurrent parasitemia was consistent with reinfection due to high, perennial malaria transmission.

Septic Embolism in a Patient with Infective Endocarditis and COVID-19

Italy has been one of the most severely affected countries by the COVID-19 pandemic, and the case fatality rate (CFR) estimated based on Italian data is one of the highest worldwide. We analyzed public data from the first 50 days of the epidemic in Italy (from February 24 to April 13, 2020) to evaluate whether evolving testing strategies and capacity could account for trends in the CFR. The CFR increased during the study period, and a significant positive correlation was found between the CFR and the percentage of positive tests among performed real-time PCR tests (positive tests % [POS%]) until March 25, suggesting the surveillance system did not detect a growing number of cases in the initial phase of the epidemic. To avoid distortion due to the delay between the identification of cases and deaths, the expected CFR (expCFR) was calculated, which represents the ratio between the predicted number of cases and deaths at the end of the epidemic based on the best fitting logistic curves of the cumulative numbers of cases and deaths. The expCFR began a downward trend from the 40th day. In the final phase, a decrease in both expCFR and POS% was identified, suggesting an improvement in surveillance. The results of this study suggest data from the first 50 days of the COVID-19 epidemic in Italy were severely affected by ascertainment bias. Insufficient testing and isolation of cases could have facilitated the widespread transmission of COVID-19 in the early stages of the outbreak.

Leptospirosis, brucellosis, and Q fever (coxiellosis) are bacterial zoonoses that cause acute febrile illness in people as well as reproductive losses in pigs. Pig keeping is an increasingly important livelihood to millions of smallholder farmers in Uganda because of exponential increases in demand for pork. The prevalence of leptospirosis and Q fever in pigs is unknown, and the few studies of porcine brucellosis have estimated a range of seroprevalence. Therefore, we undertook a prevalence survey of leptospirosis, brucellosis, and Q fever in pigs using quantitative real-time PCR to determine the potential importance of these zoonoses to the growing pig sector in Uganda. Six hundred forty-nine pigs were sampled in 2015–2016 at an urban pork slaughterhouse. Ten percent of pigs (n = 68) had leptospiral DNA in either their kidney or reproductive tissue. In adjusted analyses, variables predictive of leptospiral status included female sex (odds ratio [OR]: 2.37, P < 0.01) and pigs sampled in March 2016 (OR: 2.23, P = 0.02) and October 2016 (OR: 0.30, P = 0.04). DNA fingerprinting revealed circulation of at least four distinct serovars in these pigs. Brucella spp. and Coxiella burnetii DNA were not detected in any sampled pig. This is the first report of widespread circulation of pathogenic Leptospira spp. in pigs in Uganda, suggesting that leptospirosis likely has a greater impact on the health of pigs than was previously recognized. Pig farmers, pig traders, and slaughterhouse workers may be at greatest occupational risk because of their direct contact with infective leptospires in aborted fetuses, bodily fluids, and other tissues.

The Swat district, a conflict-hit territory due to Taliban militancy, had a damaged local health infrastructure. Animal-bite injuries leading to rabies is one of the major health concerns in developing countries, especially within conflict zones. The current prospective epidemiological study was conducted to estimate the cumulative incidence of animal-bite injuries, to summarize characteristics of bite victims and biting animals, and to collect information about post-exposure prophylaxis (PEP) practices in Swat district, Pakistan, during 2014. A questionnaire was designed to collect data about the sociodemography of the patients, bite incident situation (provoked or unprovoked), injury pattern, animal type, PEP, and vaccination. Descriptive analyses were conducted using bar graphs, frequency tables, and chi-square tests were used to determine associations. The cumulative incidence of animal-bite injuries was 39 per 100,000 people during the study period (May–August 2014). The majority of incidents were reported from rural regions (77.7%) and were males (76.6%) younger than 10 years (37.3%). Dogs were the most frequent biting animal (86.8%) followed by rats (4.7%). About 77.7% patients washed their wound before arrival at hospital. After an eclipse phase of 10 days, 44 (10.1%) animals developed sign of rabies. The current study has highlighted a topic of interest for health, education, veterinary, and local government policy makers regarding prevention of animal bites, benefits of PEP, vaccination of human and domestic animals, control of stray dogs, and eradication of rabies in developing countries with damaged healthcare structures.

We calculated carbon emissions associated with air travel of 4,834 participants at the 2019 annual conference of the American Society of Tropical Medicine and Hygiene (ASTMH). Together, participants traveled a total of 27.7 million miles or 44.6 million kilometers. This equates to 58 return trips to the moon. Estimated carbon dioxide equivalent (CO2e) emissions were 8,646 metric tons or the total weekly carbon footprint of approximately 9,366 average American households. These emissions contribute to climate change and thus may exacerbate many of the global diseases that conference attendees seek to combat. Options to reduce conference travel–associated emissions include 1) alternating in-person and online conferences, 2) offering a hybrid in-person/online conference, and 3) decentralizing the conference with multiple conference venues. Decentralized ASTMH conferences may allow for up to 64% reduction in travel distance and 58% reduction in CO2e emissions. Given the urgency of the climate crisis and the clear association between global warming and global health, ways to reduce carbon emissions should be considered.

Something Big that Matters: The American Society of Tropical Medicine and Hygiene’s Commitment to Combat Climate Change

Bartonella henselae is a zoonotic Gram-negative Bacillus associated with self-limited regional lymphadenopathy. In recent decades, an expanding spectrum of clinical manifestations has been described, in part, due to improved diagnostics. However, updated epidemiological data are sparse. We retrospectively reviewed the clinical features of 31 patients with B. henselae infection older than 15 years from 2005 to 2019, in the tropical Top End of Australia. Our annual disease incidence of 1.3 cases per 100,000 population is lower than that in the national database surveillances in the United States, but the hospitalization incidence of 0.9 per 100,000 population in our region is higher than those reported in the literature, with an average length of stay of 9 days. Patients were more commonly male, aboriginal, and aged less than 14 years (median age: 7 years), living in a rural setting with presentation during our monsoon season. The disease spectrum included lymph node disease (74%), organ peliosis, endocarditis, cutaneous lesions, parapharyngeal abscess, parotitis, and neurologic and ocular syndromes. Lymph node disease was far commoner in children than the more serious systemic B. henselae infections associated with adults (P = 0.074). Although no deaths were reported, significant morbidities were observed. Two endocarditis cases presented with glomerulonephritis, and hematological and neurological features mimicking vasculitis, and consequently received immunosuppressants. One case was only diagnosed after representation with serial embolic strokes. Given the heterogeneity of disease manifestations with nonspecific symptoms and significant consequences, a timely and accurate diagnosis is needed to avoid unnecessary treatments or interventions.

Poor food hygiene practices, child feces not being disposed of in a latrine, child mouthing of contaminated fomites, and poor hand hygiene of caregivers have been associated with diarrheal diseases, environmental enteropathy, and impaired growth in young children. Mobile health (mHealth) programs present a low-cost approach to delivering water, sanitation, and hygiene (WASH) programs. We conducted a theory-driven and evidence-based approach to formative research and intervention development to design and pilot test a Baby WASH mHealth program targeting food hygiene, child mouthing, and child feces disposal behaviors in urban Dhaka, Bangladesh. Formative research activities included 31 semi-structured interviews, five group discussions, six mHealth workshops, and a three-phase iterative pilot study among 102 households. Findings from semi-structured interviews and group discussions indicate that caregivers of young children have relatively high awareness of the need for safer food hygiene, child mouthing, and child feces disposal practices, but are limited by existing household responsibilities and restricted access to enabling technology that would facilitate practicing recommended behaviors. The piloted Baby WASH mHealth program was well-received by households. This study presents a theory-driven and evidence-based approach for intervention development that can be implemented for the development of future WASH mHealth programs in low-resource settings.