The American Journal of Tropical Medicine and Hygiene - Current Issue

Catastrophic damage and floods followed the deadliest cyclone on record for the Southern Hemisphere. In the aftermath of Cyclone Idai, a cholera outbreak was detected. The global stockpile of oral cholera vaccine was rapidly deployed to counter this fast-growing epidemic. We urge the international community to continue to highlight the importance of water, sanitation, and hygiene as the long-term goal for controlling cholera and meeting the 2030 Sustainable Development Goals.

Ethiopia’s hepatitis C virus (HCV) prevalence is predicted to rise by 2030. To halt this increasing trend, a suitable approach to the elimination of HCV is needed. This review explores the current status, challenges, and opportunities and outlines a strategy for the micro-elimination approach in Ethiopia. I searched PubMed and EMBASE using combined Medical Subject Heading databases for the literature on HCV micro-elimination. A phased public health approach to HCV micro-elimination, including preparation/capacity building (phase I), implementation (phase II), and rollout and scale-up (phase III), targeting people living with HIV, prisoners, chronic hepatitis and cancer patients, blood donors, and pregnant women is a pragmatic strategy to Ethiopia. This can be implemented at general and tertiary care referral hospitals with a future scale-up to district hospitals through task-shifting by training general practitioners, nurses, laboratory technologists, and pharmacists. Availability of the highly effective direct-acting antivirals (DAAs) can be ensured by expanding the existing program that provides highly subsidized DAAs through an agreement with Gilead Sciences, Inc. and eventually aiming at domestic generic manufacturing. The significant enablers to HCV micro-elimination in Ethiopia include the control of healthcare–associated HCV infection, blood safety, access to affordable testing and pan-genotypic DAAs, task-shifting, multisectoral partnership, and regulatory support. General population-based HCV screening and treatment are not cost-effective for Ethiopia because of high cost, program complexity, and disease epidemiology.

Aedes mosquitoes are the principal dengue vector in Taiwan, where the use of insecticides is a key element in the national control strategy. However, control efforts are constrained by the development of resistance to most insecticides, including pyrethroids. In this study, mutations in the voltage-gated sodium channel (VGSC) gene resulting in knockdown resistance (kdr) were examined in Aedes aegypti. Fragments of the VGSC gene were polymerase chain reaction (PCR)-amplified followed by restriction fragment length polymorphism analysis in samples from various settings in Southern Taiwan covering dry and wet seasons from 2013 to 2015. Three kdr mutations were identified: V1023G, D1794Y, and F1534C, with observed frequencies of 0.36, 0.55, and 0.33, respectively, in the dry season of 2013–2014. Exploring for temporal changes, the most important observation was the 1534C allele frequency increment in the following season to 0.60 (P < 0.05). This study suggests that continued insecticide pressure is driving the mutational changes, although the selection is ambiguous in the mosquito population.

Perceived exposure to mosquitoes plays a fundamental role in the adoption of a range of protective behaviors aiming to prevent and control mosquito-borne disease. However, it is largely unknown in the present literature to what extent perceived exposure is associated with actual exposure. Moreover, the perception of nuisance may depend on the natural environment in which human populations are living, and especially its epidemiological context. In this study, the hypothesis that perceived exposure is driven by mosquito abundance was tested in two different geographic areas. We compared a range of perceived nuisance measures—collected through questionnaires—with egg number measured within ovitraps located in the south of France, which has been recently colonized by an arbovirus vector, and La Martinique island, a tropical French territory, which has a long history of outbreaks of mosquito-borne pathogens. Unexpectedly, only the nuisance due to mosquito noise was correlated with ovitrap activity in southern France. All other perceived exposure measures, both in the south of France and in Martinique, were not correlated with egg number surrounding households investigated. These results suggest the existence of habituation effects that may disturb the engagement in adaptive behaviors in the face of change in the entomological conditions.

It remains uncertain why most infectious disease mortalities disappeared before modern medical interventions. Historical epidemiology using prospectively collected U.S. Army data from the Civil War (1860–1861), Spanish–American War (1898–1899), and First World War (1917–1918) suggests that epidemiological isolation was a major mortality risk factor for soldiers. Morbidity and mortality due to common infections decreased progressively from 1860 to 1918, except for influenza during the 1918 pandemic. Adult measles or mumps infections are indicative of isolated rural populations and correlated with disease mortality by U.S. state. Experiencing infections before adulthood may equip the immune system to better resist infections and decrease mortality rates.

Hundreds of thousands of children continue to die each year from diarrhea. We piloted a low-cost liquid chlorine point-of-use (POU) water treatment among elementary school children in Bangladesh. We began the 1-month intervention in four schools (two urban and two rural) by introducing POU drinking water hardware and behavior change communication. We trained teachers to deliver sessions encouraging students to drink chlorinated water from their own small plastic bottles to avoid disease transmission. We used cue cards and flip charts as visual aids. We evaluated the acceptability, feasibility, and potential for sustainability after 1 month and after 14 months of the intervention. During 1-month follow-up, among 141 drinking events observed, 141 students (100%) drank chlorinated water. In 93 or 66% of events, students used their own bottles, and in 43 (30%) of the events, they used common cups or hands washed before drinking. During the 14-month follow-up, we observed 732 drinking events. In 653 of 732 events (89%), students drank chlorinated water; in 78 events (11%), they consumed water from untreated drinking water sources. Among those who consumed chlorinated water, 20% (131/653) used their own bottles to drink water, 72% (467/653) used common cups, and 8% (55/653) used both hands to drink water. Most stated that they drank chlorinated water because it is safe, it has health benefits, and treatment reduces germs. Introduction of specific hardware, weekly hygiene sessions, and education materials enabled schools to treat water at POU and students to consume treated water.

This study was performed to examine whether prenatal lipid-based nutrient supplementation is an effective means of improving birth outcomes compared with other types of supplementation including iron folic acid (IFA), United Nations multiple micronutrient preparation (UNIMAP), other multiple micronutrients (MMN), and fortified corn–soy blend (CSB). A meta-analysis was performed to determine the relative risks and mean differences in birth outcomes between prenatal lipid-based nutrients versus prenatal IFA, UNIMAP, other MMN, and CSB in randomized controlled trials. Eleven databases, including PubMed (MEDLINE), were searched. Study quality was assessed using the Cochrane Collaboration’s tool for assessing the risk of bias. Fifty-eight overall good-quality studies extracted from 11 eligible articles with 101,553 mother–baby pairs were included. Lipid-based nutrient supplementation significantly reduced the risks of low birthweight, small for gestational age, and stunting (n = 5, 5, and 4, respectively) and significantly increased the means of birthweight, birth length, arm circumference, and weight-for-age z-score (n = 5, 5, 4, and 3, respectively). Lipid-based nutrient supplementation did not significantly reduce the risk of preterm birth, stillbirth, abortion, perinatal death, or underweight (n = 5, 5, 5, 3, or 3, respectively) or significantly increase the mean of head circumference or height-for-age z-score (n = 4 or 2, respectively). In conclusion, the results supported the efficacy of prenatal lipid-based nutrient supplementation compared with IFA, UNIMAP, other MMN, and CSB for reducing the risk of small birth size.

Between 1990 and 2015, Kenya had a 0.9% annual reduction in maternal mortality, one of the lowest reductions globally. This slow decline was linked to the relatively low utilization of delivery services. We designed a mobile phone–enhanced 24-hour transport navigation system coupled with personalized and interactive gestation-based text messages (MAccess) to address maternal child health service utilization. The primary purpose of this analysis is to explore the ways in which pregnant and postnatal women made decisions regarding care-seeking for pregnancy and childbirth services, the processes of getting care from home to the hospital as well their perceptions on how the MAccess intervention affected their pregnancy and childbirth care-seeking and utilization experience. We conducted semistructured, individual interviews with 18 postpartum women. Participants were purposively sampled. Interviews were audiotaped, transcribed, and analyzed using thematic analysis. For participants in this study, all three delays interacted in a complex manner to affect women’s utilization of pregnancy and childbirth services. Even though women were aware of the benefits of skilled birth attendance, other health system factors such as opening hours, or health workers’ attitudes still deterred women from delivering in health facilities. The MAccess innovation was highly acceptable to women throughout pregnancy and childbirth and helped them navigate the complex and layered individual, infrastructural, and health system factors that put them at risk of adverse maternal and newborn outcomes. These findings emphasize that an integrated approach, which addresses all delays simultaneously, is important for reducing perinatal morbidity and mortality.

Stunting, defined as height-for-age Z score equal to or lower than −2, is associated with increased childhood mortality, cognitive impairment, and chronic diseases. The aim of the study was to investigate the relationship between linear growth, intestinal damage, and systemic inflammation in infants at risk of stunting. We followed up 78 infants aged 5–12 months living in rural areas of Peru for 6 months. Blood samples for biomarkers of intestinal damage (intestinal fatty-acid–binding protein [I-FABP] and zonulin) and systemic inflammation (interleukin-1β, interleukin-6, tumor necrosis factor α [TNF-α], soluble CD14, and lipopolysaccharide-binding protein [LBP]) and fecal samples for microbiome analysis were collected at baseline and closure of the study. The children’s growth and health status were monitored through biweekly home visits by trained staff. Twenty-one percent of the children became stunted: compared with non-stunted children, they had worse nutritional parameters and higher levels of serum I-FABP at baseline. The likelihood of becoming stunted was strongly associated with an increase in sCD14 over time; LBP and TNF-α showed a trend toward increase in stunted children but not in controls. The fecal microbiota composition of stunted children had an increased beta diversity compared with that of healthy controls throughout the study. The relative abundance of Ruminococcus 1 and 2, Clostridium sensu stricto, and Collinsella increased in children becoming stunted but not in controls, whereas Providencia abundance decreased. In conclusion, stunting in our population was preceded by an increase in markers of enterocyte turnover and differences in the fecal microbiota and was associated with increasing levels of systemic inflammation markers.

Although the issue of substandard and falsified medicines is quite well known, most research has focused on medicines used to treat communicable diseases, and relatively little research has been carried out on the quality of medicines for noncommunicable diseases (NCDs). This study was designed to assess the quality of seven widely used medicines for NCDs in Cambodia during 2011–2013. Medicines were collected from private community drug outlets in Phnom Penh (urban area), by stratified random sampling and in Battambang, Kandal, Kampong Speu, and Takeo (rural areas) by convenience sampling. Samples were subsequently analyzed by visual inspection, authenticity investigation, and pharmacopoeial analysis by high-performance liquid chromatography. Various discrepancies were observed in visual inspection of packages and medicines. Of 372 tablet/capsule samples from 64 manufacturers in 16 countries, the manufacturers confirmed 107 (28.8%) as authentic; the authenticity of other samples could not be verified. Three hundred sixty-four (97.8%) samples were registered in Cambodia. Among all samples, 23.4% (95% CI 19.2–28.0) were noncompliant in one or more of the quality tests: 12.9% (95% CI 9.7–16.7) contained an amount of active pharmaceutical ingredient outside the permitted range, including some showing extreme deviations, 14% (95% CI 10.6–17.9) failed because of content variation, and 10.8% (95% CI 7.8–14.4) failed to meet pharmacopoeial reference ranges in dissolution tests. Pharmaceutical quality appeared to be unrelated to storage conditions. Although no sample was obviously falsified, there is a high prevalence of substandard medicines for NCDs in Cambodia, indicating the need for focused regulatory action, including collaborative initiatives with manufacturers.

In this study, we report on the prevalence of 19 virulence genes in enteroaggregative Escherichia coli (EAEC) isolates from northern South Africa. Stool samples obtained prospectively from 97 children from 1 to 12 months of age were analyzed, and EAEC isolates were confirmed based on the presence of aaiC or aatA genes. We investigated 177 enteroaggregative Escherichia coli isolates for the prevalence of virulence genes using multiplex polymerase chain reaction. The chromosomal gene aaiC was detected at higher frequency (48.0%) compared with aatA (26.0%). The gene encoding the open reading frame Orf61 was the most prevalent putative virulence trait detected among the isolates (150/177; 84.7%). None of the genes was statistically associated with diarrhea (P > 0.05). Detection rates were higher during 7–12 month of life with an association observed for the pic gene and the age group 7–12 months (P = 0.04). Winter was the season with the highest detection rates. Our data reveal a high prevalence of Orf61, Orf3, and astA in South African EAEC isolates. Specific genes may provide additional markers for the study of disease associations with age and season of sample collection.

Pneumonia, as defined by WHO, is a syndromic diagnosis characterized by presence of cough or difficult breathing. Presentation to health-care provider depends on timely identification of signs and symptoms by caretakers. We explored patterns of health-care utilization among caretakers of a randomly selected sample of 1,152 children aged 2–59 months, residing in low-income settlements of Karachi, Pakistan. Information on household demographics, occurrence of pneumonia-specific symptoms, care seeking, air quality, and knowledge regarding preventive measures for pneumonia was collected. Predictors of care seeking were estimated using weighted logistic regression. Prevalence of pneumonia with cough and rapid or difficulty in breathing was found to be 40.8% and 37.1% in infants (2–11 months) and children (12–59 months), respectively. Ninety-five percentage of caretakers sought care, 68.5% privately. Odds ratios (ORs) for independent predictors of care-seeking were as follows: younger age of child (infants compared with children), 3.60 (95% CI = 2.65–4.87); caretaker with primary education compared with none, 3.40 (2.46–4.70); vaccine awareness, 1.65 (1.45–1.87); and breastfeeding awareness, 1.32 (1.13–1.53). Presence of symptoms such as fever OR, 1.51 (1.30–1.76); tachypnea, 1.57 (1.35–1.83); chest indrawing, 2.56 (2.05–3.18); persistent vomiting, 1.69 (1.37–2.09); and recurrent illness, 2.57 (2.23–2.97) were also predictive. There is high health-care utilization for pneumonia with the skewed presentation toward private services. Strategies should be focused on making pneumonia care standardized, efficient and affordable, especially in the private sector.

Antimicrobial resistance (AMR) is a growing threat to global health. Although AMR endangers continued effectiveness of antibiotics, the impact of AMR has been poorly estimated in low-income countries. This study sought to quantify the effect of AMR on treatments for pediatric pneumococcal disease in Ethiopia. We developed the DREAMR (Dynamic Representation of the Economics of AMR) model that simulate children younger than 5 years who acquire pneumococcal disease (pneumonia, meningitis, and acute otitis media) and seek treatment from various health facilities in Ethiopia over a year. We examined the AMR levels of three antibiotics (penicillin, amoxicillin, and ceftriaxone), treatment failures, and attributable deaths. We used the cost-of-illness method to assess the resulting economic impact of AMR from a societal perspective by estimating the direct and indirect treatment costs and productivity losses. Findings showed that AMR against antibiotics that were used to treat pneumococcal disease led to 195,763 treatment failures per year, which contributed to 2,925 child deaths annually in Ethiopia. Antimicrobial resistance resulted in a first-line treatment failure rate of 29.4%. In 1 year, the proportion of nonsusceptible Streptococcus pneumoniae bacteria increased by 2.1% and 0.5% for amoxicillin and penicillin, and reduced by 0.3% for less commonly used ceftriaxone. Annual costs of AMR to treat pneumococcal disease were around US$15.8 million, including US$3.3 million for ineffective first-line treatments, US$3.7 million for second-line treatments, and US$8.9 million for long-term productivity losses. Antibiotic stewardship to reduce misuse and overuse of antibiotics is essential to maintain the effectiveness of antibiotics, and lessen the health and economic burden of AMR.

We report a case of acute rheumatic fever with severe pancarditis occurring simultaneously with probable acute post-streptococcal glomerulonephritis in a previously well, Australian Aboriginal, 29-year-old male. These autoimmune streptococcal sequelae are usually considered pathogenetically distinct, and concurrence has not previously been reported from this high-burden setting. We hypothesize that a single type of infecting group A Streptococcus (Strep A) triggered both autoimmune sequelae. Salient features included mitral and aortic regurgitation that worsened during the acute illness, painful pericarditis, and high troponin; severe acute kidney injury with oliguria, hematuria, and macroalbuminuria; reduced complement (C3); and elevated streptococcal serology. The case highlights important diagnostic and management challenges. It also illustrates the serious morbidity impact of the complications of Strep A.

Leprosy reactions are immune-mediated complications occurring in up to 50% of patients. The immune consequences of helminth infections and micronutrient deficiencies suggest a potential role in type 1 reactions (T1R) or type 2 reactions (T2R). We conducted a case–control study in Minas Gerais, Brazil, to evaluate whether comorbidities and other factors are associated with reactions in patients with multibacillary leprosy. Stool and serum were tested for helminth infections. Deficiencies of vitamin A, D, and iron were measured using serum retinol, 25-hydroxyvitamin D, and ferritin, respectively. Logistic regression models identified associations between reactions and helminth infections, micronutrient deficiencies, and other variables. Seventy-three patients were enrolled, 24 (33%) with T1R, 21 (29%) with T2R, 8 (15%) with mixed T1R/T2R, and 20 (27%) without reactions. Evidence of helminth infections were found in 11 participants (15%) and included IgG4 reactivity against Schistosoma mansoni, Strongyloides, and Ascaris antigens. Thirty-eight (52%) had vitamin D deficiency, eight (11%) had vitamin A insufficiency, 21 (29%) had anemia, and one (1.4%) had iron deficiency. Multivariable logistic regression showed no statistically significant associations between helminth coinfections and total reactions (adjusted odds ratios [aOR]: 1.36, 95% CI: 0.22, 8.33), T1R (aOR: 0.85, 95% CI: 0.17, 4.17), or T2R (aOR: 2.41, 95% CI: 0.29, 20.0). Vitamin D deficiency and vitamin A insufficiency were also not statistically associated with reactions. However, vitamin deficiencies and helminth infections were prevalent in these patients, suggesting a potential role for additional treatment interventions. Studying reactions prospectively may further clarify the role of comorbidities in the clinical presentation of leprosy.

Disseminated nontuberculous mycobacterial (NTM) infections usually occur in severely immunosuppressed patients. These infections may also occur in previously immunocompetent patients with acquired anti–interferon-gamma antibodies (anti–IFN-γ Abs). A previously healthy 33-year-old man presented with a 3-week history of cough and fever. Chest computed tomography showed air-space consolidation in the middle lobe of the right lung and enlargement of the supraclavicular, mediastinal, and hilar lymph nodes. Tissue samples obtained via mediastinoscopy showed granuloma formation with acid-fast bacteria; cultures from the tissue revealed Mycobacterium kansasii. Accordingly, a diagnosis of disseminated M. kansasii disease was made. The positive control tested negative in the QuantiFERON-TB Gold In-tube test, suggesting the presence of anti–IFN-γ Abs. The ELISA test for anti–IFN-γ Abs demonstrated an increased titer. Antimycobacterial drug treatments were initiated after diagnosis. His symptoms improved over 2 months, and he remains well on outpatient management. Disseminated M. kansasii disease is a very rare condition suggestive of immunosuppression. Testing for anti–IFN-γ antibodies might be important in all cases of disseminated M. kansasii disease.

Genitourinary tuberculosis (TB) is a rare but well-described form of extrapulmonary TB. We present a case of a 35-year-old man from Ethiopia with scrotal swelling and fever who was found to have epididymo-orchitis due to Mycobacterium tuberculosis. The patient presented to the hospital multiple times before undergoing operative debridement with fine needle aspiration and tissue biopsy to confirm the diagnosis. He improved with antituberculous therapy. Patients with TB risk factors presenting with epididymitis that is refractory to empiric antibiotic therapy warrant consideration of TB epididymitis. Our case demonstrates the high index of suspicion required to establish a diagnosis of genitourinary TB.