The American Journal of Tropical Medicine and Hygiene - Online First

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 (StrepA) 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 StrepA.

Strongyloidiasis, caused by Strongyloides stercoralis infection, is an important neglected tropical disease that causes significant public health problems in the tropics and subtropics. The disease can persist in hosts for decades and may be life-threatening because of hyperinfection and dissemination. Ivermectin (mostly) and albendazole are the most common anthelmintics used for treatment. Albendazole is suboptimal for this parasite, and although ivermectin is quite effective in immunocompromised patients, a multiple-course regimen is required. Furthermore, reliance on a single drug class for treating intestinal nematodes is a recipe for future failure. Therefore, it is important to discover new anthelmintics to treat or prevent human strongyloidiasis. One promising candidate is the Bacillus thuringiensis crystal protein Cry5B. Cry5B is highly potent against parasitic nematodes, for example, hookworms and Ascaris suum. Here, we investigated the potential of Cry5B against S. stercoralis. Multiple stages of S. stercoralis, including the first larval stage (L1s), infective stage (iL3s), free-living adult stage, and parasitic female stage, were all susceptible to Cry5B as indicated by impairment of motility and decreased viability in vitro. In summary, Cry5B demonstrated strong potential as an effective anthelmintic for treatment and transmission control of human strongyloidiasis, justifying further experiments to investigate in vivo therapeutic efficacy.

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.

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. Ten 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, 4, 5, and 4, 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 2, 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.

Ethiopia’s hepatitis 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 health care–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.

Intravenous (IV) dexamethasone is recommended for 14 days in stage 1 and 28 days in stage 2/3 tuberculous meningitis (TBM). We used a different steroid protocol. We shifted TBM patients to oral steroids after 48 hours of sustained improvement on IV steroids (oral group). Patients who worsened after shifting to oral steroids were reinitiated on IV steroids. Once they showed a consistent improvement for 48 hours, the IV steroids were overlapped with oral steroids for 7–10 days to taper off IV steroids (overlap group). We compared total IV steroid days in our patients with the recommended treatment and identified predictors that favored the oral group. This was a retrospective study. We included 98 patients with TBM (66 in the overlap group and 32 in the oral group) from January 2013 to July 2018. The median IV steroid days were 9 days (interquartile range of 4–12; 2–3.5 days in the oral group and 10–11.5 days in the overlap group). The mortality rate was 6.1%. The logistic regression model showed that TBM patients with basal exudate, tuberculoma, and modified Rankin scale (mRS) > 3 had a higher probability for going to the oral group. We conclude that total IV steroid days can be reduced in TBM patients by our method of steroid use. Presence of basal exudates and tuberculoma may favor early shifting from IV to oral steroid, whereas higher mRS may require a relatively longer course of IV steroid.

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.

The discovery and characterization of novel parasite antigens to improve the diagnosis of Trypanosoma cruzi by serological methods and for accurate and rapid follow-up of treatment efficiency are still needed. TcTASV is a T. cruzi–specific multigene family, whose products are expressed on the parasite stages present in the vertebrate host. In a previous work, a mix of antigens from subfamilies TcTASV-A and TcTASV-C (Mix A + C) was sensitive and specific to identify dogs with active infection of high epidemiological relevance. Here, TcTASV-A and TcTASV-C were assayed separately as well as together (Mix A + C) in an ELISA format on human samples. The Mix A + C presented moderate sensitivity (78%) but high diagnostic accuracy with a 100% of specificity, evaluated on healthy, leishmaniasic, and Strongyloides stercoralis infected patients. Moreover, antibody levels of pediatric patients showed—2 years posttreatment—diminished reactivity against the Mix A + C (P < 0.0001), pointing TcTASV antigens as promising tools for treatment follow-up.

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.

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.