The American Journal of Tropical Medicine and Hygiene - Current Issue

The value of baseline entomological data to any future area-wide release campaign relies on the application of consistent methods to produce results comparable across different times and places in a stepwise progression to larger releases. Traditionally, standard operating procedures (SOPs) and operational plans support this consistency and, thus, the validity of emergent data. When release plans include transgenic mosquitoes for vector control or other novel beneficial insects, additional factors come into play such as biosafety permits, stakeholder acceptance, and ethics approval, which require even greater coordination and thoroughness. An audit approach was developed to verify the correct use of SOPs and appropriate performance of tasks during mosquito mark, release, recapture (MRR) studies. Audit questions matched SOPs, permit terms and conditions, and other key criteria, and can be used to support subsequent “spot check” verification by field teams. An external team of auditors, however, was found to be effective for initial checks in this example before the use of a transgenic strain of laboratory mosquitoes. We recommend similar approaches for field studies using release of novel beneficial insects, to ensure useful and valid data as an outcome and to support confidence in the rigor of the step-wise process.

Schistosomiasis is an acute and chronic parasitic disease caused by blood flukes of the genus Schistosoma. More than 220 million people worldwide were estimated to have active schistosomiasis in 2017, 90% of whom live on the African continent, but only 102 million were reported to have received treatment. Africa is also disproportionately burdened by HIV, with an estimated 26 million people living with HIV in 2017. Given these overlapping epidemics, we conducted a systematic review to ascertain the contribution of schistosomes to HIV acquisition risk, the contribution of HIV to schistosome acquisition, the impact of HIV on schistosomiasis-related morbidity, the impact of schistosomes on HIV disease progression and immune response, the impact of HIV on the efficacy of praziquantel treatment, and the impact of HIV on egg shedding. We reviewed studies of people living in sub-Saharan Africa coinfected with HIV and Schistosoma spp. between January 1996 and July 2018. We found that 1) infection with Schistosoma haematobium increases the risk of HIV acquisition, 2) there is currently a lack of data on whether HIV infection increases the risk of Schistosoma acquisition, 3a) HIV coinfection was not an accelerating factor for adverse Schistosoma outcomes, 3b) schistosomiasis may be an important contributor to immune activation in HIV coinfected people, 4) praziquantel use in coinfected people may improve immune reconstitution on antiretroviral therapy for HIV, and 5) there is evidence that HIV infection reduces egg excretion in individuals infected with Schistosoma mansoni.

The tenth conference of the African Society of Human Genetics was held in Egypt with the theme “Human Genetics and Genomics in Africa: Challenges for Both Rare and Common Genetic Disorders.” Current research was presented, and we discussed visions for the future of genomic research on the African continent. In this report, we summarize the presented scientific research within and relevant to Africa as presented by both African and non-African scientists. We also discuss the current situation concerning genomic medicine and genomic research within the continent, difficulties in implementing genetic services and genomic medicine in Africa, and a road map to overcome those difficulties and meet the needs of the African researchers and patients.

The ongoing transmission of leprosy in India is worrisome, and emerging drug resistance may be one of the factors responsible for the continued transmission of leprosy in India. Emerging cases of multidrug-resistant Mycobacterium leprae pose a great threat to eradication of leprosy and must be addressed with utmost priority. We report a case of multidrug-resistant M. leprae in a case of relapse where slit skin smear (SSS) was negative and histopathology was inconclusive. Drug resistance studies in leprosy are undertaken only in smear-positive relapse cases, and detection of this type of multidrug resistance in a case with negative SSS and innocuous histopathology is rather unusual and highlights the importance of undertaking drug resistance tests even in smear-negative cases of leprosy relapse. Resistance to ofloxacin (OFL) is also a cause for concern as OFL is one of the reserve drugs recommended for treatment of rifampicin-resistant strains.

In this study, we report an investigation of a tuberculosis (TB) outbreak in a high school in China. Eleven students with active TB were identified. A culture-negative 17-year-old girl was considered as index case affected by pulmonary and meningeal TB. Screening results indicated latent TB in 32.8% of the students in the classroom of index case, whereas a significantly decreased prevalence of TB infection was found among students on the same floor, ranging from 1.3 to 8.2%. Genotyping revealed that all the Mycobacterium tuberculosis (MTB) isolates belonged to Beijing spoligotype international types 1 (SIT1). In conclusion, a diagnostic delay for the culture-negative index case played an important role in the transmission of Beijing genotype MTB strain in the boarding school in Yunnan. The separate locations of classrooms and sufficient air ventilation contributed to the significant difference in proportions of TB infection between classmates and other students in this outbreak.

Pneumonia remains a leading cause of morbidity and mortality in young children. The total cost of pneumonia-related hospitalization, including household-level cost, is poorly understood. To better understand this burden in an urban setting in South America, we incorporated a cost study into a trial assessing zinc supplements in treatment of severe pneumonia among children aged 2–59 months at a public hospital in Quito, Ecuador, which provides such treatment at no charge. Data were collected from children’s caregivers at hospitalization and discharge on out-of-pocket payments for medical and nonmedical items, and on employment and lost work time. Analyses encompassed three categories: direct medical costs, direct nonmedical costs, and indirect costs, which covered foregone wages (from caregivers’ self-reported lost earnings) and opportunity cost of caregivers’ lost time (based on the unskilled labor wage in Ecuador). Caregivers of 153 children completed all questionnaires. Overall, 57% of children were aged less than 12 months, and 46% were female. Just over 50% of mothers and fathers had completed middle school. Most reported direct costs, which averaged $33. Most also reported indirect costs, the mean of which was $74. Fifty-seven reported lost earnings (mean = $79); 29 reported lost time (estimated mean cost = $37). Stratified analyses revealed similar costs for children < 12 months and ≥ 12 months, with variations for specific items. Costs for hospital-based treatment of severe pneumonia in young children represent a major burden for households in low- to middle-income settings, even when such treatment is intended to be provided at no cost.

Eye-to-eye transmission of Chlamydia trachomatis, the causative agent of trachoma, may be plausibly interrupted if faces are kept free of ocular and nasal discharge. Between April and June 2018, 83 children aged 1–9 years with active trachoma were recruited from 62 households and allocated to a face cleaning protocol: face washing with water, face washing with water and soap, or face wiping. Faces were examined for the presence of ocular and nasal discharge, and swabs were taken from faces and hands to test for C. trachomatis at baseline, immediately post protocol, and after 1, 2, and 4 hours (washing protocols). Washing with soap was more effective at removing ocular discharge than either washing with water (89% and 27% of discharge removed, respectively, P = 0.003) or wiping with a hand (42%, P = 0.013). The reduction in prevalence of ocular discharge was sustained for at least four hours. The prevalence of C. trachomatis on face swabs was reduced by all washing protocols. The importance of soap should not be overlooked during facial cleanliness promotion.

Typhoid conjugate vaccines represent a new tool for typhoid control. However, incidence data are needed to inform decisions about introduction. We sought to estimate typhoid and paratyphoid fever incidence in Vientiane, the capital and largest city of the Lao People’s Democratic Republic (Lao PDR). We did a representative cluster survey of health-seeking behavior for fever in Vientiane from January 15, 2019 through January 26, 2019. Multipliers derived from the survey were applied to data from Salmonella Typhi and Salmonella Paratyphi A bloodstream infection surveillance from Mahosot Hospital, Vientiane, for the period of January 1, 2015 through December 31, 2017, to estimate enteric fever incidence. A total of 336 households representing 1,740 persons were enrolled in the healthcare utilization survey, and multipliers were derived based on responses to questions about healthcare seeking in the event of febrile illness. Of 7,997 Vientiane residents receiving blood cultures over the 2-year surveillance period at Mahosot Hospital, we identified 16 (0.2%) with Salmonella Typhi and six (< 0.1%) with Salmonella Paratyphi A bloodstream infection. After applying multipliers, we estimated that the annual incidence of typhoid was 4.7 per 100,000 persons and paratyphoid was 0.5 per 100,000 persons. During the study period, the incidence of typhoid and paratyphoid fever was low in Vientiane. Ongoing surveillance is warranted to identify increases in future years. Similar studies elsewhere in the Lao PDR would be useful to understand the wider enteric fever situation in the country.

Although typhoid is endemic to Southeast Asia, very little is known about the disease in Laos. Typhoid vaccination is not included in the national immunization program. Although sanitation has improved, one million people still do not have access to basic clean water sources. We describe the epidemiology and antimicrobial susceptibility patterns of Salmonella enterica serovar Typhi (S. Typhi) infection in Laos based on isolates accrued over 18 years at Mahosot Hospital, Vientiane. All blood cultures collected from patients presenting with fever submitted to the Microbiology Laboratory at Mahosot Hospital (February 2000–December 2018) were included. This included patients from Vientiane and four provincial hospitals and one typhoid outbreak investigation. A total of 913 (1.5%) of 60,384 blood cultures were positive for S. Typhi. The majority of isolates with data available (712/898, 79.3%) were susceptible to all antibiotics tested, with 59 (6.5%) multidrug-resistant (MDR) isolates, mostly from one outbreak. Of 854 isolates, 12 (1.4%) were fluoroquinolone resistant. Patient admissions peaked between March and June at the end of the dry season. Although there are key limitations, these data give the first detailed epidemiological evidence of typhoid in Laos. However, estimates will be greatly influenced by access to blood culture services and health-seeking behavior. Although typhoid multidrug resistance and fluoroquinolone resistance are not currently major issues in Laos, continued surveillance and improved antibiotic stewardship are necessary to forestall worsening of the situation. Cost-effectiveness analysis is needed to inform decisions regarding typhoid vaccine introduction.

Kala azar occurs among seasonal and migrant agricultural workers in northwest Ethiopia and accounts for almost 60% of the disease burden in the country. We conducted a quantitative study on the level of knowledge and practice of this vulnerable group in relation to kala azar transmission and acceptability of its vector control tools. A total of 403 workers were randomly selected from eight farms using a purposive sampling technique. Knowledge and practice scores were calculated based on 12 and 9 core questions, respectively. Binary logistic regression was used to identify factors associated with knowledge and practice. A large gap in knowledge of the disease and the vector was evident with 61.8%, 24.6%, and 13.6% of the workers having poor, moderate, and good levels of knowledge scores, respectively. Similarly, 95% of the seasonal workers reported poor level of use of protective measures against the bite of the sand fly vector. Good level of knowledge about kala azar and its sand fly vector was statistically associated with formal education (adjusted odds ratio [AOR] = 2.11; 95% CI = 1.17, 3.80; P < 0.05) and previous exposure to health education (AOR = 4.72; 95% CI = 1.99, 11.16; P < 0.001). Despite poor current knowledge and practice, a large proportion of the study participants showed interest in using vector control tools if made available, with 78% of the seasonal and migrant workers expressing some willingness to pay for different measures that can protect against sand fly bites. Therefore, we strongly recommend that comprehensive health education and vector control programs should be provided to these workers.

After the first autochthonous case of cutaneous leishmaniasis was reported in the Atlántico department in the Caribbean region of Colombia, entomological sampling was conducted in the specific areas where the infection might have occurred. CDC traps were installed inside and outside dwellings in the peri-urban and rural areas of a settlement in the municipality of Luruaco. Sampling was performed during the night with protected human bait, and phlebotomine sand flies were actively sampled from potential diurnal resting sites within dwellings. Ten species of the genus Lutzomyia were identified; Lutzomyia evansi was the dominant species (78%) in the rural and peri-urban areas as well as in the different sampled habitats, followed by Lutzomyia panamensis and Lutzomyia gomezi. There was a 100% household infestation by Lu. evansi, and its indoor mean abundance was 13.3 sand flies/CDC trap/night. The indoor mean abundance of Lu. panamensis and Lu. gomezi was only 0.9 and 0.8 sand flies/CDC trap/night, respectively. Female Lu. evansi were collected with protected human bait, mostly in the peridomestic area, with sustained activity during the night and a slight increase in the activity from 19:00 to 23:00 hours. Of the total sand flies captured in the diurnal resting sites, 73.1% were collected from the walls of bedrooms and corresponded to Lu. evansi, Lutzomyia cayennensis cayennensis, and Lutzomyia trinidadensis. Owing to their vectorial importance, the species on which entomological surveillance should be focused are Lu. evansi, Lu. panamensis, and Lu. gomezi. The biting and resting behavior reported in this study will help guide vector prevention and the control of leishmaniasis within the study area.

Cutaneous leishmaniasis (CL) caused by Leishmania braziliensis occurs predominantly in adult males. Herein, we compare the clinical presentation and the response to antimony therapy of CL in children versus adults. Participants included 571 patients with CL; of these, 129 were children (age ≤ 12 years). Cure was defined as the complete healing of ulcer in the absence of raised borders at day 90 after initiation of therapy. Failure was defined by the presence of an active ulcer or a scar with elevated borders at day 90. In comparison with adults, children had shorter duration of illness, more lesions in the head, and smaller ulcers. Risk factors for therapeutic failure were younger age, shorter duration of disease, higher number of lesions, and larger size of the biggest ulcer. When age was categorized in ≤ 12-year-olds (children versus adults), it predicted therapeutic failure with statistical significance at day 60 but not at day 90. In conclusion, our data indicate that there are significant differences in the clinical presentation of CL between children and adults. Physicians caring for children with CL should be aware that lesions may take longer to heal and remain alert for the possibility of higher odds of therapeutic failure in this group.

Currently, a significantly lower temperature (35°C) than initially established (56°C) is indicated as the maximum temperature storage for the commercial reference visceral leishmaniasis (VL) freeze-dried direct agglutination test (FD-DAT). Despite an approximately 50% loss in the number of promastigotes in an FD-DAT batch that expired 7 years earlier, the promastigotes maintained a similar morphology to the equivalent valid batch implying most likely that auto-agglutination, rather than aging, is the main reason for expiry. The substitution of normal saline which was initially recommended for reconstitution, by citrate-saline/formaldehyde (CSF) as an anti-clumping/preservative agent resulted in restoration of validity comparable with that of the freeze-dried original or the liquid direct agglutination test (LQ-DAT) version (Friedman ANOVA test = 1.0588; P = 0.5890). Following a similar reconstitution procedure as for the 7-year expired antigen, using significantly lower promastigote concentration (1.4 × 107/mL) than in the non-expired (9.0 × 107/mL), good reliability for VL detection and stability at 4°C (> 12 months) were achieved. In comparison with the original version using normal saline ($32.0/vial), the cost-effectiveness of the FD-DAT was appreciably improved by the CSF incorporation and lowering of promastigote concentration per unit suspension medium ($12.8/vial). With diagnostic reliability comparable with the full-out titration used, FD-DAT procedure based on single sample dilution at the VL cutoff (1:3,200) permitted the use of significantly smaller antigen volumes (0.1 mL vs. > 1.5 mL), therefore contributing to a further reduction in the application cost. The successful replacement of β-mercaptoethanol (β-ME) by urea (T = 21.00; P = 0.0868) provided the required safety for the test procedure similar to the widely applied LQ-DAT.

The direct agglutination test (DAT) for visceral leishmaniasis (VL) is the serodiagnostic test for VL that has the most robust sensitivity and specificity in the field across all endemic regions. It is based on trypsin-treated and formaldehyde-fixed whole promastigote cells from Leishmania donovani. The exact identity and nature of the epitopes on the DAT antigen that cause agglutination with VL patients’ sera are currently unknown. In this study, we performed antigen-inhibition studies which revealed that lipophosphoglycan (LPG) and the DAT antigen share epitopes. Antibody inhibition with a monoclonal antibody directed against the phosphoglycan repeat epitope of LPG showed that this is not the epitope that reacts with human sera. Oxidation of carbohydrates by sodium metaperiodate did not alter the reactivity of human sera with the DAT antigen and LPG. This indicates that carbohydrates do not play a role in the reaction of the DAT antigen with antibodies in serum from VL patients, and that they also are not involved in the reaction of LPG with the same serum. We conclude that the noncarbohydrate moiety of LPG, that is, the core–anchor fragment, and potentially other noncarbohydrate epitopes on the surface of the DAT antigen are responsible for its agglutination with antibodies from VL patients. As LPG plays a role in the DAT reaction, this could facilitate the following: 1) incorporation of LPG, preferably the synthetic version of the core–anchor fragment, into an immunochromatographic test format that is more adapted as a point-of-care test (short incubation, little training, and equipment needed) than DAT and 2) enhancing the quality control for the production of the DAT antigen.

Chronic Chagas heart disease has different clinical manifestations including arrhythmias, heart failure, and stroke. Chest pain is one of the most common symptoms and when associated with changes in the electrocardiogram, such as T-wave changes, electrically inactive areas, and segmental wall motion abnormalities, may lead to a misdiagnosis of acute coronary syndrome (ACS). Here, we describe two patients with Chagas heart disease and syncope due to sustained ventricular tachycardia who were misdiagnosed with ACS, and discuss the role of novel imaging modalities in the differential diagnosis and risk stratification.

Chagas is a neglected disease endemic in Latin America. Vector transmission control had been aggressively performed. Recent entomological surveillance in Brazil has revealed natural infection rates ranging from 0.40% to 0.52%. Although serological surveys are complex to develop, they are important for disease control. In this study, we validated the use of saliva in ELISA commercial kits with a cohort of 100 patients with Chagas disease followed at Hospital das Clinicas in São Paulo, Brazil, and 50 healthy controls. Five ELISA kits for detecting antibodies against Trypanosoma cruzi were tested. The best discrimination between Chagas patients and controls was observed with the Wiener kit, which yielded a sensitivity of 97% and a specificity of 100%. Our findings reveal that the use of saliva may be an alternative to large-scale screening surveys in detecting T. cruzi antibodies; it is a noninvasive sample collection method potentially key to large-scale screening in children.

As China moves to the prevention of reestablishment of malaria, maintaining skills for malaria in county personnel on the “1-3-7” surveillance and response strategy is critical. China’s “1-3-7” strategy defines targets used to guide and monitor malaria case reporting, investigation, and response, respectively: reporting of malaria cases within 1 day, their confirmation and investigation within 3 days, and the appropriate public health response to prevent further transmission within 7 days. Assessing the knowledge of local CDC malaria personnel on the “1-3-7” surveillance and response strategy is urgently needed. In June 2016, two different training modules (classroom-style teaching and tabletop exercises) were conducted for 125 CDC staff in Jiangsu Province, China, to determine the effectiveness of the two training modules on CDC staff knowledge and learning of the “1-3-7” strategy. The classroom-style training module just imparted the malaria knowledge to participants through teaching. Tabletop exercises were carried out through discussion-based scenarios using questions and answers on the “1-3-7” strategy. Questionnaires assessing knowledge improvement were designed and administered to personnel responsible for malaria surveillance and response activities, including at baseline and end line. Overall, knowledge of the “1-3-7” strategy for malaria elimination was 63.2% correct at baseline, 70.6% after implementing a classroom-style teaching module (χ2 = 11.20, P = 0.001), and 84.6% after the tabletop exercise module (χ2 = 48.82, P < 0.001). The knowledge of each component of the “1-3-7” strategy improved significantly after the tabletop exercise module. The total proportion of respondents with a high score (greater than or equal to 75%) was 82.7% in the classroom-style module and 95.2% in the tabletop exercise module. The proportion of respondents with a high score significantly increased after tabletop exercises in the stratified demographic groups of men who work at the county CDC level, have a bachelor’s degree, hold a professional title as professor or assistant, are aged 31–50 years, and have attained 11–20 years of service with the CDC compared with the classroom-style module. Acceptability of the classroom-style module (78.2%) compared with tabletop exercises (94.4%) by the CDC malaria personnel increased significantly (χ2 = 11.96, P = 0.004). Feedback from participants on the modules suggest the tabletop exercises were an effective training method, which could maintain and improve the knowledge and capacity for malaria surveillance and response in basic CDC level personnel in China.