The American Journal of Tropical Medicine and Hygiene - Current Issue

Snakebite primarily affects rural subsistent farming populations in underdeveloped and developing nations. The annual number of deaths (100,000) and physical disabilities (400,000) of snakebite victims is a societal tragedy that poses a significant added socioeconomic burden to the society. Antivenom therapy is the treatment of choice for snakebite but, as testified by the continuing high rates of mortality and morbidity, too many rural tropical snakebite victims fail to access effective treatment. Here, we advocate for more basic research to better understand the pathogenesis of systemic and local envenoming and describe how research outcomes can identify novel snakebite therapeutic strategies with the potential to be more accessible and affordable to victims than current treatment.

Schistosomiasis is traditionally classified into an acute and a chronic phase, although a precise temporal distinction between the two phases has not been established. Lung involvement can be observed in both phases. We previously reported seven cases of pulmonary lesions due to chronic schistosomiasis in African immigrants. All cases were documented with CT scans and demonstrated complete resolution after treatment with praziquantel. Moreover, another case showed spontaneous disappearance of the nodule before treatment with praziquantel. These findings are similar to those observed in the acute phase of schistosomiasis, with well-defined or ground glass nodules that resolve spontaneously. According to these findings, we postulate the presence of an “intermediate” phase of schistosomiasis involving the lungs that can be defined as an “early chronic phase,” and presents analogies to the acute phase. We also hypothesize that in the “early chronic phase,” the female worms transit through the lungs where they may lay eggs. These passages not only cause transient, but also radiologically visible alterations. The pathophysiology of lung lesions in the late chronic phase is probably different: the adult worms settled in the mesenteric plexuses produce eggs for years. The eggs repeatedly migrate to the perialveolar capillary beds via portal-caval shunting. Thus, in this case it is the eggs and not the adult worms that reach the lungs in a scattered way. Based on our findings, we suggest the alternative hypothesis that the pulmonary involvement is a phase of the natural evolution of the infection, both from Schistosoma mansoni and Schistosoma haematobium.

The current strategy used by many funding agencies for determining how money is spent on research to help prevent infectious disease outbreaks is based on pathogen-specific priority lists. Listing disease threats provides focus for business and research planning conducive to specific goals of developing a drug, or a vaccine, or other particular product. But, this singular type of focus has consequences. This perspective explores the consequences of lists, and describes how parallel programming independent of disease lists that address what we need to do to prevent and mitigate emerging disease risks may provide benefits out of reach of a singular focus on what products we need to have.

Brett-Major and others remind us that pathogen lists for emerging infectious diseases aid in the development of tools that target specific pathogens (e.g., vaccines) and help attract financial support. These lists tell us what we need to have, not what we need to do. The authors call for more research on ways to prevent these diseases (e.g., platform technologies for vaccines) and mitigate disease impact. Vaccines and new treatments that target individual pathogens have many limitations. However, we might save lives by treating patients with inexpensive generic drugs that target common features of the host response to infection. Undertaking research on this approach to treatment is what we need to do.

Falsified and substandard medicines are associated with tens of thousands of deaths, mainly in young children in poor countries. Poor-quality drugs exact an annual economic toll of up to US$200 billion and contribute to the increasing peril of antimicrobial resistance. The WHO has emerged recently as the global leader in the battle against poor-quality drugs, and pharmaceutical companies have increased their roles in assuring the integrity of drug supply chains. Despite advances in drug quality surveillance and detection technology, more efforts are urgently required in research, policy, and field monitoring to halt the pandemic of bad drugs. In addition to strengthening international and national pharmaceutical governance, in part by national implementation of the Model Law on Medicines and Crime, a quantifiable Sustainable Development Goal target and an international convention to insure drug quality and safety are urgent priorities.

Acute post-streptococcal glomerulonephritis (APSGN) is a postinfectious immune-mediated kidney disease associated with group A Streptococcus (GAS). The prevalence of APSGN varies within and between countries and is influenced by socioeconomic, host, and bacterial factors. The disease is more prevalent in developing countries and resource-poor settings of developed countries, such as the Indigenous populations residing in tropical Australia. The M-protein is a universally present GAS surface antigen that is the focus of molecular typing and vaccine research. Early reports suggested that some M-proteins (emm types) are more likely to cause APSGN than others. Here, we present the first systematic review of the global distribution of APSGN-associated GAS emm types. There were 46 emm types among the 676 cases described in 15 reviewed articles. Only 43% APSGN cases would have had theoretical coverage from the experimental M protein-based GAS vaccine. Vaccine coverage was higher in regions such as North America (97%) and the United Kingdom (98%) than Africa (67%) and Australia (38%). Variable vaccine coverage against APSGN- associated emm types highlights the need for further research into this disease, particularly in settings of poverty, where APSGN prevalence is higher. Three GAS emm types (emm49, emm60, and emm55) consistently occur in APSGN cases around the world. Future studies would therefore benefit from examining the genomic epidemiology of these emm types to unravel potential markers of APSGN.

Leptospirosis is a global zoonotic disease caused by pathogenic bacteria of the Leptospira genus, which are fastidious, slow-growing organisms. Antimicrobial susceptibility data are limited; traditionally, the organisms have not been culturable on solid media. The recent development of Leptospira Vanaporn Wuthiekanun (LVW) agar, which facilitates rapid growth of Leptospira spp., provides the opportunity for antimicrobial susceptibility testing. Eighty-three Leptospira spp. clinical isolates originating from patients in Laos between 2006 and 2016 were tested against six antimicrobials (azithromycin, ceftriaxone, ciprofloxacin, doxycycline, gentamicin, and penicillin G) using disk diffusion on LVW agar. Quality control was undertaken using American Type Culture Collection (ATCC) reference strains with known susceptibilities on both standard media and LVW agar. All Leptospira spp. isolates produced large zones of inhibition around each of the six antimicrobials. All zones were greater than 25 mm: gentamicin produced the smallest zones (median 35 mm; interquartile range 30 mm–37 mm) and azithromycin produced the largest zones (median 85 mm; interquartile range 85 mm–85 mm). Zones produced by non-leptospiral ATCC reference strains on LVW agar were within 2 mm of accepted strain-specific quality control range on standard media. Antimicrobial activity on LVW agar appears to be similar to that on standard media. As there are no published susceptibility guidelines for the Leptospira genus, zone interpretation was subjective. Leptospira Vanaporn Wuthiekanun agar enabled antimicrobial susceptibility testing of multiple Leptospira isolates on solid media; the large zone sizes observed suggest that resistance has not emerged to these six antimicrobials in Lao Leptospira spp.

Leptospirosis is a neglected zoonotic bacterial disease caused by pathogenic Leptospira spp. Only limited studies have been conducted on the presence of Leptospira spp. in rats in Antananarivo, the capital city of Madagascar. We assessed Leptospira prevalence in small mammals in urban areas of Antananarivo where sanitation is inadequate and there is risk of flooding during the rainy season. We captured rodents and shrews at two sites and examined kidney samples from 114 animals using culture and a real-time polymerase chain reaction (PCR) assay specific to pathogenic Leptospira spp. We identified 23 positive samples containing Leptospira interrogans and Leptospira borgpetersenii, with a high prevalence in Rattus norvegicus (44.9%). Our results indicate that small mammals, in particular R. norvegicus, present a major public health risk for acquiring leptospirosis in Antananarivo.

Melioidosis is a tropical infection, first described in Myanmar but now rarely diagnosed there, which is widespread in Southeast Asia. The infection is predominantly acquired by people and animals through contact with soil or water. This study aimed to detect the causative organism, Burkholderia pseudomallei, in environmental samples from farms in Thanlyin and Hmawbi townships near Yangon, Myanmar. One hundred and twenty soil samples and 12 water samples were collected and processed using standard microbiological methods. Burkholderia species were isolated from 50 of the 120 (42%) soil samples but none of the water samples. Arabinose assimilation was tested to differentiate between B. pseudomallei and the nonpathogenic Burkholderia thailandensis, and seven of 50 isolates (14%) were negative. These were all confirmed as B. pseudomallei by a species-specific multiplex polymerase chain reaction (PCR). This is the first study to detect environmental B. pseudomallei in Myanmar and confirms that melioidosis is still endemic in the Yangon area.

Thromobocytopenia predicts mortality in patients with melioidosis in Thailand. We analyzed platelet counts in two large cohorts of melioidosis patients in tropical northern Australia to assess utility in a different clinical setting. Admission platelet counts were compared between subgroups of patients with different clinical outcomes. Patients with more severe disease (indicated by bacteremia, septic shock, and death) had significantly lower platelet counts than those with less severe disease. Logistic regression analysis was carried out for potential predictors of mortality among various clinical parameters, and platelet count was shown to be an independent predictor of mortality. Furthermore, in patients critically ill with melioidosis, an increasing platelet count after admission was associated with a significantly greater chance of survival. However, given that most patients with severe disease still had platelet counts within the normal range, platelet count is not a useful biomarker for predicting the severity of melioidosis in a clinical context.

A comprehensive targeted intervention (CTI) was designed and deployed in the neighborhoods of cholera cases in the Kathmandu Valley with the intent of reducing rates among the neighbors of the case. This was a feasibility study to determine whether clinical centers, laboratories, and field teams were able to mount a rapid, community-based response to a case within 2 days of hospital admission. Daily line listings were requested from 15 participating hospitals during the monsoon season, and a single case initiated the CTI. A standard case definition was used: acute watery diarrhea, with or without vomiting, in a patient aged 1 year or older. Rapid diagnostic tests and bacterial culture were used for confirmation. The strategy included household investigation of cases; water testing; water, sanitation, and hygiene (WASH) intervention; and health education. A CTI coverage survey was conducted 8 months postintervention. From June to December of 2016, 169 cases of Vibrio cholerae O1 were confirmed by bacterial culture. Average time to culture result was 3 days. On average, the CTI Rapid Response Team (RRT) was able to visit households 1.7 days after the culture result was received from the hospital (3.9 days from hospital admission). Coverage of WASH and health behavior messaging campaigns were 30.2% in the target areas. Recipients of the intervention were more likely to have knowledge of cholera symptoms, treatment, and prevention than non-recipients. Although the RRT were able to investigate cases at the household within 2 days of a positive culture result, the study identified several constraints that limited a truly rapid response.

Data regarding cardiac involvement in enteric fever among travelers are scarce. In this retrospective study, 59 patients were hospitalized with enteric fever during 2004–2017 and 28 had cardiac workups. Among those, four had evidence of cardiac involvement, including clinical myocarditis, electrocardiogram changes, or troponin elevation. Cardiac involvement was higher among patients infected with Salmonella Typhi than with Salmonella Paratyphi A (P = 0.08), with a significant relative risk of 6 (95% CI: 1.15–31.22, P = 0.03). Time from symptoms onset to effective treatment was longer for patients with cardiac involvement (13 versus 7.15 days, P < 0.05). It seems that cardiac involvement in enteric fever is not uncommon in travelers. Such involvement seems to be more common in patients with delay of effective treatment to the second week of illness. Although fatal or complicated cases are rare in travelers, the cardiac complication may be an important contributor to morbidity and mortality in this group.

Although access to piped drinking water continues to increase globally, information on the prevalence and clonal composition of coliforms found in piped water systems in low-resource settings remains limited. From June to July 2016, we examined Escherichia coli isolates in domestic water from the distribution system in Alibag, a small town in India. We analyzed the isolates for drug resistance and genotyped them by multilocus sequence typing. Of 147 water samples, 51 contained coliforms, and 19 (37%) of the 51 were biochemically confirmed to contain E. coli. These samples contained 104 E. coli isolates—all resistant to ampicillin. Resistance to ceftazidime was observed in 52 (50%) isolates, cefotaxime in 59 (57%), sulfamethoxazole–trimethoprim in 46 (44%), ciprofloxacin in 30 (29%), and gentamicin in two (2%). Thirty-eight (36%) belonged to sequence types recognized as extraintestinal pathogenic E. coli (ExPEC); 19 (50%) of these 38 ExPEC belonged to known uropathogenic E. coli lineages. This exploratory field research shows the extent to which “improved” drinking water is a potential source of E. coli strains capable of causing extraintestinal infections.

Mass drug administration (MDA) for trachoma control using azithromycin has generated concern for the development of resistant organisms. However, the contribution from azithromycin available in local pharmacies has not been studied. In Kilosa district, Tanzania, MDA stopped over 4 years ago, and this study sought to determine the availability of azithromycin in local pharmacies and correlate it with azithromycin resistance in children born after MDA. A cross-sectional survey was conducted in 644 randomly selected hamlets in Kilosa district, in which the presence of a pharmacy and the availability of azithromycin and erythromycin were determined. In 30 randomly selected hamlets, a random sample of 60 children less than 5 years were tested for azithromycin-resistant Streptococcus pneumoniae (Spn) and Escherichia coli (Ec), from nasopharyngeal and rectal swabs, based on disk diffusion criteria. Only 26.6% of hamlets had a pharmacy. Azithromycin and erythromycin were available in 30.8% and 89.1% of pharmacies closest to the hamlets, respectively. In the 30 communities tested for resistance, the overall prevalence of azithromycin-resistant Spn isolates was 14%. Six of seven (87%) hamlets where azithromycin was available had resistant Spn, compared with 14 of 23 (61%) hamlets without availability. Similarly, six of seven (87%) hamlets where azithromycin was available had resistant Ec isolates compared with 21 of 23 (70%) hamlets without availability. However, the differences were not statistically significant (P = 0.46 and 0.49, respectively). The availability of azithromycin in pharmacies in the district was limited, and a strong correlation with azithromycin-resistant Spn or Ec was not observed.

Antibiotic-resistant bacterial infections are a major public health problem, and children in low-resource settings represent a particularly high-risk group. Few data are available on the dynamics of and risk factors for gastrointestinal carriage of antibiotic-resistant bacteria in these vulnerable populations. In this study, we described the antibiotic susceptibility profiles of Escherichia coli isolated from stool specimens collected from children aged 6 to 60 months enrolled in a birth cohort study in Haydom, Tanzania. We estimated the association between sociodemographic risk factors, child illnesses, and antibiotic exposure and E. coli drug resistance. Carriage of antibiotic-resistant E. coli was common starting early in life and did not clearly increase with age. The majority of isolates were resistant to ampicillin (749/837; 89.5%), cefazolin (742/837; 88.6%), and cotrimoxazole (721/837; 86.1%). Resistance to amoxicillin/clavulanate (361/836; 43.2%), ampicillin/sulbactam (178/819; 21.7%), nalidixic acid (131/831; 15.8%), and azithromycin (115/837; 13.7%) was also seen. Only 1.8% (15/837) of the pooled E. coli isolates met the criteria for extended-spectrum beta-lactamase production. High antibiotic use (0.26 additional resistant antibiotic classes; 95% CI: 0.05, 0.47) and high income (0.28 additional resistant antibiotic classes; 95% CI: 0.06, 0.50) were associated with the carriage of antibiotic-resistant E. coli, whereas hospital birth, crowding in the home, improved drinking water and sanitation, and common childhood illnesses were not. In this setting, the carriage of antibiotic-resistant E. coli was common. Other than recent antibiotic exposure and high income, individual risk factors for the acquisition and carriage of resistance could not be identified, suggesting that population-level interventions are needed.