Telemedicine and Pediatric Care in Rural and Remote Areas of Middle-and-Low-Income Countries: Narrative Review.

OBJECTIVES: Caring for children in low- and middle-income countries (LMIC) can be challenging. This review article aims to explore role of telemedicine in supporting pediatric care in LMIC. METHODOLOGY: A narrative review of existing English and Spanish literature was conducted to assess role of telemedicine to support pediatric care in LMIC. RESULTS: Beside medical education and direct pediatric care, telemedicine can provide sub-specialties consultations without extra burden on families. Additionally, telemedicine can help in lowering under-5 mortality by supporting neonatal care, infectious illnesses, and non-communicable diseases (NCDs). Telemedicine can be a gate for universal coverage for all children at a lower cost. For over a decade, it has been implemented successfully and sustained in a few LMIC. However, challenges in implementing telemedicine are enormous. Still, opportunities arise by using simpler technology, low-width band internet, smartphones, instant messaging applications and solar energy. COVID-19 pandemic facilitated acceptance and applicability of telemedicine worldwide including LMIC. Nevertheless, governments must regulate telemedicine by issuing policies and ensuring employment of local experts when possible to meet local resources and cultural competency. CONCLUSION: Telemedicine has proven successful in improving pediatrics care. Many LMIC should take advantage of this innovation to promote equity and access to high quality pediatric care.

Evaluation of three alternatives cost-effective culture media for Mycobacterium tuberculosis detection and drug susceptibility determination using the microscopic observation drug susceptibility (MODS) assay.

Tuberculosis phenotypic detection assays are commonly used in low-resource countries. Therefore, reliable detection methods are crucial for early diagnosis and treatment. The microscopic observation drug susceptibility (MODS) assay is a culture-based test to detect Mycobacterium tuberculosis and characterize drug resistance in 7-10 days directly from sputum. The use of MODS is limited by the availability of supplies necessary for preparing the enriched culture. In this study, we evaluated three dry culture media that are easier to produce and cheaper than the standard one used in MODS [1]: an unsterilized powder-based mixed (Boldú et al., 2007) [2], a sterile-lyophilized medium, and (Sengstake et al., 2017) [3] an irradiated powder-based mixed. Mycobacterial growth and drug susceptibility were evaluated for rifampin, isoniazid, and pyrazinamide (PZA). The alternative cultures were evaluated using 282 sputum samples with positive acid-fast smears. No significant differences were observed in the positivity test rates. The positivity time showed high correlations (Rho) of 0.925, 0.889, and 0.866 between each of the three alternative media and the standard. Susceptibility testing for MDR and PZA showed an excellent concordance of 1 compared to the reference test. These results demonstrate that dry culture media are appropriate and advantageous for use in MODS in low-resource settings.

Porcine model of neurocysticercosis by intracarotid injection of Taenia solium oncospheres: Dose assessment, infection outcomes and serological responses.

BACKGROUND: Neurocysticercosis (NCC) is the infection of the human central nervous system (CNS) by Taenia solium larvae that cause significant neurological morbidity. Studies on NCC pathophysiology, host-parasite interactions or therapeutic agents are limited by the lack of suitable animal models. We have previously reported that carotid injection of activated T. solium oncospheres directs parasites into the CNS and consistently reproduces NCC. This study assessed the minimal dose required to consistently obtain NCC by intracarotid oncosphere injection and compared antigen and antibody response profiles by dose-group. METHODS/PRINCIPAL FINDINGS: Three groups of pigs were infected with either 2500 (n = 10), 5000 (n = 11), or 10000 (n = 10) oncospheres. Two pigs died during the study. Necropsy exam at day 150 post-infection (PI) demonstrated viable NCC in 21/29 pigs (72.4%), with higher NCC rates with increasing oncosphere doses (4/9 [44.4%], 9/11 [81.8%] and 8/9 [88.9%] for 2500, 5000, and 10000 oncospheres respectively, P for trend = 0.035). CNS cyst burden was also higher in pigs with increasing doses (P for trend = 0.008). Viable and degenerated muscle cysticerci were also found in all pigs, with degenerated cysticerci more frequent in the 2500 oncosphere dose-group. All pigs were positive for circulating parasite antigens on ELISA (Ag-ELISA) from day 14 PI; circulating antigens markedly increased at day 30 PI and remained high with plateau levels in pigs infected with either 5000 or 10000 oncospheres, but not in pigs infected with 2500 oncospheres. Specific antibodies appeared at day 30 PI and were not different between dose-groups. CONCLUSION/SIGNIFICANCE: Intracarotid injection of 5000 or more oncospheres produces high NCC rates in pigs with CNS cyst burdens like those usually found in human NCC, making this model appropriate for studies on the pathogenesis of NCC and the effects of antiparasitic treatment.

Alternative cost-effective media to facilitate MODS culture for diagnostics of tuberculosis.

Most culture-based methods for tuberculosis diagnosis remain low-cost options for low- and mid-income countries. The MODS culture is a rapid and low-cost assay to diagnose tuberculosis and determine drug susceptibility. However, its implementation is limited due to the low accessibility to supplies required for the enriched medium. In this study, we evaluate two alternative culture media: A powder-based mixed (PM) and a lyophilized media (LM). Catalase, PANTA, and gamma irradiation were evaluated as additions to PM and LM. The culture performance of the alternative media was compared with the standard MODS medium (MM) using Mycobacterium tuberculosis isolates and positive acid-fast smear sputum samples. Overall, no significant difference was observed in the bacterial growth between PM and LM with MM. However, PANTA and gamma irradiation combined reduced bacterial growth significantly in all media variants. A median positivity day of 6 ± 5 days was observed for sputum samples, regardless of the culture medium. The preliminary results show that the two variants culture media have a similar performance to the standard MODS medium. The powder-based media with PANTA (PM_P) showed a time-to-positivity and sensitivity similar to the standard MODS medium. It is the simplest to prepare and does not require any sterilization process.

Antibiotic Use and Resistance Knowledge Assessment of Personnel on Chicken Farms with High Levels of Antimicrobial Resistance: A Cross-Sectional Survey in Ica, Peru.

Poultry farming represents Peru's primary food animal production industry, where antimicrobial growth promoters are still commonly used, exerting selective pressure on intestinal microbial populations. Consumption and direct animal-to-human transmission have been reported, and farmworkers are at high risk of colonization with resistant bacteria. We conducted a cross-sectional survey among 54 farmworkers to understand their current antimicrobial resistance (AMR) awareness in Ica, Peru. To gain insight into the potential work-related risk of exposure to bacteria, we also measured the AMR rates in Escherichia coli isolated among 50 broiler chickens. Farmworkers were unaware of antimicrobial resistance (31.5%) or antibiotic resistance (16.7%) terms. Almost two-thirds (61%) consumed antibiotics during the previous month, and only 42.6% received a prescription from a healthcare professional. A total of 107 E. coli chicken isolates were obtained, showing a high frequency of multidrug-resistant (89.7%) and extended-spectrum beta-lactamase (ESBL) production (71.9%). Among ESBL-producer isolates, 84.4% carried the blaCTX-M gene. Results identified gaps in knowledge that reflect the need for interventions to increase antimicrobial awareness among poultry farmworkers. The high AMR rates among E. coli isolates highlight the need to reduce antimicrobial use in poultry farms. Our findings reveal a critical need for effective policy development and antimicrobial stewardship interventions in poultry production in Ica, Peru.

Low-cost 3D-printed inverted microscope to detect Mycobacterium tuberculosis in a MODS culture.

MODS, an assay for diagnosis of tuberculosis and drug-susceptibility, is based in the microscopic observation of the characteristic cords of Mycobacterium tuberculosis colonies grown in liquid media. An inverted optical microscope (100× magnification) is required to observe and interpret MODS cultures. Unfortunately, the cost of commercial inverted microscopes is not affordable in low resource settings. To perform a diagnosis of tuberculosis using the MODS assay, images with modest quality are enough for proper interpretation. Therefore, the use of a high cost commercial inverted optical microscope is not indispensable. In this study, we designed a prototype of an optical inverted microscope created by 3D-printing and based on a smartphone. The system was evaluated with 226 MODS TB positive and 207 MODS TB negative digital images. These images were obtained from 10 sputum samples MODS positive and 10 sputum samples MODS negative. The quality of all images was assessed by a qualified technician, in terms of adequacy to interpret and classify them as positive or negative for tuberculosis. The quality of the images was considered appropriate for MODS interpretation. All the 20 samples were correctly classified (as TB positive/negative) by reading with the prototype 3D-printed inverted microscope.

Vulnerable families and costly formula: a qualitative exploration of infant formula purchasing among peri-urban Peruvian households.

BACKGROUND: Substantial evidence exists surrounding the health risks of breast milk substitutes (BMS) in place of exclusive breastfeeding among infants < 6 months of age in resource-poor settings. Yet, mothers' experiences of selecting and purchasing BMS brands have not been well studied to date. This qualitative study explored the factors influencing BMS purchasing practices, along with the consequences of those decisions, in peri-urban Lima, Peru. METHODS: We conducted in-depth interviews (IDIs) with 29 mothers who had begun mixed-feeding their infants during the first 6 months of life. Interviews explored participants' reasons for initiating infant formula use and their experiences of selecting, purchasing, and providing BMS to their children. Audio recordings were transcribed, coded, and key themes and illustrative vignettes were identified. RESULTS: The primary reported reasons for initiating infant formula use included having received a recommendation for infant formula from a healthcare provider, concerns about an infant's weight gain, and the perception of insufficient breast milk. Mothers tended to initially purchase the BMS brand that had been recommended by a doctor, which was often more expensive than the alternatives. The costs of BMS, which escalated as infants grew, often disrupted the household economy and generated significant stress. While some mothers identified alternatives allowing them to continue purchasing the same brand, others chose to switch to less expensive products. Several mothers began to feed their infants follow-on formula or commercial milk, despite their awareness that such practices were not recommended for infants under 6 months of age. The approval of family members and the absence of an infant's immediate adverse reaction influenced mothers' decisions to continue purchasing these products. CONCLUSIONS: The high costs of BMS may deepen existing socio-economic vulnerabilities and generate new risks for infant health. The continued dedication of resources towards breastfeeding education and support is critical, and strategies would benefit from underscoring the long-term financial and health consequences of infant formula use, and from strengthening women's self-efficacy to refuse to initiate infant formula when recommended. In addition, health providers should be trained in counseling to help women to relactate or return to exclusive breastfeeding after cessation.

The genetic structure and adaptation of Andean highlanders and Amazonians are influenced by the interplay between geography and culture.

Western South America was one of the worldwide cradles of civilization. The well-known Inca Empire was the tip of the iceberg of an evolutionary process that started 11,000 to 14,000 years ago. Genetic data from 18 Peruvian populations reveal the following: 1) The between-population homogenization of the central southern Andes and its differentiation with respect to Amazonian populations of similar latitudes do not extend northward. Instead, longitudinal gene flow between the northern coast of Peru, Andes, and Amazonia accompanied cultural and socioeconomic interactions revealed by archeology. This pattern recapitulates the environmental and cultural differentiation between the fertile north, where altitudes are lower, and the arid south, where the Andes are higher, acting as a genetic barrier between the sharply different environments of the Andes and Amazonia. 2) The genetic homogenization between the populations of the arid Andes is not only due to migrations during the Inca Empire or the subsequent colonial period. It started at least during the earlier expansion of the Wari Empire (600 to 1,000 years before present). 3) This demographic history allowed for cases of positive natural selection in the high and arid Andes vs. the low Amazon tropical forest: in the Andes, a putative enhancer in HAND2-AS1 (heart and neural crest derivatives expressed 2 antisense RNA1, a noncoding gene related to cardiovascular function) and rs269868-C/Ser1067 in DUOX2 (dual oxidase 2, related to thyroid function and innate immunity) genes and, in the Amazon, the gene encoding for the CD45 protein, essential for antigen recognition by T and B lymphocytes in viral-host interaction.

Application of a cost-effectiveness analysis of pathogen-specific vaccines against gastroenteritis to a military population in a developing country setting.

Vaccine implementation planning in low- and middle-income countries (LMIC) often focuses on children without considering special adult populations. We adapted an economic model developed by the United States Department of Defense (DoD) to evaluate the cost-effectiveness of vaccine acquisition strategies for Campylobacter-, ETEC-, Shigella-, and norovirus-associated gastroenteritis. We compared implementation costs with current medical management in the Peruvian armed forces, a special population of low- and middle-income (LMIC) adults with a high incidence of infectious gastroenteritis. Pathogen-specific vaccine implementation resulted in calculated cost-effectiveness ratio (CER) per duty day lost averted (CERDDL) of $13,741; $1,272; $301; and $803, and a CER per diarrhea day averted of $2,130; $215; $51; and $199 for Campylobacter, ETEC, Shigella, and norovirus, respectively. These estimates compare favorably to CERDDL estimates from high-income military population and suggest that implementing vaccines gastroenteritis may be cost-effective in the Peruvian military population.

Severity of Chagasic Cardiomyopathy Is Associated With Response to a Novel Rapid Diagnostic Test for Trypanosoma cruzi TcII/V/VI.

Background: Trypanosoma cruzi causes Chagas disease in the Americas. The outcome of infection ranges from lifelong asymptomatic status to severe disease. Relationship between T. cruzi lineage (TcI-TcVI) infection history and prognosis is not understood. We previously described peptide-based lineage-specific enzyme-linked immunosorbent assay (ELISA) with trypomastigote small surface antigen (TSSA). Methods: A novel rapid diagnostic test (RDT; Chagas Sero K-SeT) that incorporates a peptide that corresponds to the TSSA II/V/VI common epitope was developed and validated by comparison with ELISA. Patients from Bolivia and Peru, including individuals with varying cardiac pathology, and matched mothers and neonates, were then tested using Chagas Sero K-SeT. Results: Chagas Sero K-SeT and ELISA results, with a Bolivian subset of cardiac patients, mothers, and neonates, were in accord. In adult chronic infections (n = 121), comparison of severity class A (no evidence of Chagas cardiomyopathy) with class B (electrocardiogram suggestive of Chagas cardiomyopathy) and class C/D (decreased left ventricular ejection fraction; moderate/severe Chagas cardiomyopathy) revealed a statistically significant increase in Chagas Sero K-SeT reactivity with increasing severity (χ2 for trend, 7.39; P = .007). In Peru, Chagas Sero K-SeT detected the sporadic TcII/V/VI infections. Conclusions: We developed a low cost RDT that can replace ELISA for identification of TSSA II/V/VI immunoglobulin G. Most importantly, we show that response to this RDT is associated with severity of Chagas cardiomyopathy and thus may have prognostic value. Repeated challenge with T. cruzi infection may both exacerbate disease progression and boost the immune response to the TSSApep-II/V/VI epitope.

Urine lipoarabinomannan glycan in HIV-negative patients with pulmonary tuberculosis correlates with disease severity.

An accurate urine test for pulmonary tuberculosis (TB), affecting 9.6 million patients worldwide, is critically needed for surveillance and treatment management. Past attempts failed to reliably detect the mycobacterial glycan antigen lipoarabinomannan (LAM), a marker of active TB, in HIV-negative, pulmonary TB-infected patients' urine (85% of 9.6 million patients). We apply a copper complex dye within a hydrogel nanocage that captures LAM with very high affinity, displacing interfering urine proteins. The technology was applied to study pretreatment urine from 48 Peruvian patients, all negative for HIV, with microbiologically confirmed active pulmonary TB. LAM was quantitatively measured in the urine with a sensitivity of >95% and a specificity of >80% (n = 101) in a concentration range of 14 to 2000 picograms per milliliter, as compared to non-TB, healthy and diseased, age-matched controls (evaluated by receiver operating characteristic analysis; area under the curve, 0.95; 95% confidence interval, 0.9005 to 0.9957). Urinary LAM was elevated in patients with a higher mycobacterial burden (n = 42), a higher proportion of weight loss (n = 37), or cough (n = 50). The technology can be configured in a variety of formats to detect a panel of previously undetectable very-low-abundance TB urinary analytes. Eight of nine patients who were smear-negative and culture-positive for TB tested positive for urinary LAM. This technology has broad implications for pulmonary TB screening, transmission control, and treatment management for HIV-negative patients.

A randomized controlled study of socioeconomic support to enhance tuberculosis prevention and treatment, Peru.

OBJECTIVE: To evaluate the impact of socioeconomic support on tuberculosis preventive therapy initiation in household contacts of tuberculosis patients and on treatment success in patients. METHODS: A non-blinded, household-randomized, controlled study was performed between February 2014 and June 2015 in 32 shanty towns in Peru. It included patients being treated for tuberculosis and their household contacts. Households were randomly assigned to either the standard of care provided by Peru's national tuberculosis programme (control arm) or the same standard of care plus socioeconomic support (intervention arm). Socioeconomic support comprised conditional cash transfers up to 230 United States dollars per household, community meetings and household visits. Rates of tuberculosis preventive therapy initiation and treatment success (i.e. cure or treatment completion) were compared in intervention and control arms. FINDINGS: Overall, 282 of 312 (90%) households agreed to participate: 135 in the intervention arm and 147 in the control arm. There were 410 contacts younger than 20 years: 43% in the intervention arm initiated tuberculosis preventive therapy versus 25% in the control arm (adjusted odds ratio, aOR: 2.2; 95% confidence interval, CI: 1.1-4.1). An intention-to-treat analysis showed that treatment was successful in 64% (87/135) of patients in the intervention arm versus 53% (78/147) in the control arm (unadjusted OR: 1.6; 95% CI: 1.0-2.6). These improvements were equitable, being independent of household poverty. CONCLUSION: A tuberculosis-specific, socioeconomic support intervention increased uptake of tuberculosis preventive therapy and tuberculosis treatment success and is being evaluated in the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT) project.

Toxicological, Enzymatic, and Molecular Assessment of the Insecticide Susceptibility Profile of Triatoma infestans (Hemiptera: Reduviidae, Triatominae) Populations From Rural Communities of Santa Cruz, Bolivia.

A wide range of insecticide resistance profiles has been reported across Bolivian domestic and sylvatic populations of Triatoma infestans (Klug, 1834) (Hemiptera, Reduviidae), including some with levels proven to be a threat for vector control. In this work, the insecticide profile of domestic T. infestans was studied with standardized toxicological bioassays, in an area that has not undergone consistent vector control. F1 first-instar nymphs hatched in laboratory from bugs captured in three communities from the Santa Cruz Department were evaluated with different insecticides. Moreover, the enzymatic activity of esterases and cytochrome P450 monooxygenases was measured in individual insects to evaluate the possible mechanism of metabolic resistance to pyrethroids. In addition, the DNA sequence of sodium channel gene (kdr) was screened for two point mutations associated with pyrethroid resistance previously reported in T. infestans.All populations showed reduced susceptibility to deltamethrin and α-cypermethrin, albeit the RR50 values varied significantly among them. Increased P450 monooxygenases and permethrate esterases suggest the contribution, as detoxifying mechanisms, to the observed resistance to deltamethrin in all studied populations. No individuals presented either mutation associated to resistance in the kdr gene. The level of susceptibility to α-cypermethrin, the insecticide used by the local vector control program, falls within an acceptable range to continue its use in these populations. However, the observed RR50 values evidence the possibility of selection for resistance to pyrethroids, especially to deltamethrin. Consequently, the use of pyrethroid insecticides should be closely monitored in these communities, which should be kept under entomological surveillance and sustained interventions.

Cost-effectiveness of Diagnostic Algorithms for Tuberculosis in Children Less Than 5 Years of Age.

BACKGROUND: The objective of this analysis was to assess the cost-effectiveness of TB diagnosis using microscopic observation drug susceptibility (MODS), Xpert MTB/RIF (Xpert) and empiric treatment for all patients, in addition to current clinical diagnostic practices in children less than 5 years of age in a national tuberculosis (TB) referral hospital in Uganda. METHODS: A decision analysis was conducted from the healthcare perspective, with a primary outcome of incremental cost-effectiveness expressed as cost per year of life gained (YLG). RESULTS: Cost-effectiveness of the algorithms depended strongly on 3 variables: the prevalence of TB, probability of death if TB was untreated and accuracy of existing diagnostic algorithms. Xpert and MODS had similar cost-effectiveness profiles and were preferred in settings where the prevalence of TB and probability of death from untreated TB were low. As the underlying probability of TB disease and death increased, treating all children with clinically suspected disease became more cost-effective. In settings where the probability that an untreated child will die of TB-whether a result of high prevalence of TB or high mortality from untreated TB-treating all children for TB is likely to be the most cost-effective approach until better diagnostic tests can be developed. CONCLUSIONS: The cost-effectiveness of diagnostic tools for TB in children depends on the population, natural history of untreated TB and existing diagnostic practices. In settings where the risk of TB death is high, empiric treatment of all children for TB should be considered until a more sensitive, low-cost diagnostic test is available.

Interdisciplinary Postdoctoral Training in Global Health Through a Novel Joint Project for Trainees from Diverse Disciplines: Benefits, Risks, and Observations.

Postdoctoral training programs are usually highly individualized arrangements between trainees and a limited number of senior mentors in their field, an approach that contrasts with current trends in public health education that promote interdisciplinary training to spur innovation. Herein, we describe an alternative model for postdoctoral training for a group of fellows from distinct disciplines. Fellows work with mentors from diverse fields to create a joint research project or a group of complementary projects, with the goal of developing a new device, intervention, or innovation to address a global health problem. The perceived benefits, challenges, and limitations of this team approach to interdisciplinary postdoctoral training are presented.

Colorimetric Detection of Plasmodium vivax in Urine Using MSP10 Oligonucleotides and Gold Nanoparticles.

Plasmodium vivax is the most prevalent cause of human malaria in the world and can lead to severe disease with high potential for relapse. Its genetic and geographic diversities make it challenging to control. P. vivax is understudied and to achieve control of malaria in endemic areas, a rapid, accurate, and simple diagnostic tool is necessary. In this pilot study, we found that a colorimetric system using AuNPs and MSP10 DNA detection in urine can provide fast, easy, and inexpensive identification of P. vivax. The test exhibited promising sensitivity (84%), high specificity (97%), and only mild cross-reactivity with P. falciparum (21%). It is simple to use, with a visible color change that negates the need for a spectrometer, making it suitable for use in austere conditions. Using urine eliminates the need for finger-prick, increasing both the safety profile and patient acceptance of this model.

The economic effects of supporting tuberculosis-affected households in Peru.

The End TB Strategy mandates that no tuberculosis (TB)-affected households face catastrophic costs due to TB. However, evidence is limited to evaluate socioeconomic support to achieve this change in policy and practice. The objective of the present study was to investigate the economic effects of a TB-specific socioeconomic intervention.The setting was 32 shantytown communities in Peru. The participants were from households of consecutive TB patients throughout TB treatment administered by the national TB programme. The intervention consisted of social support through household visits and community meetings, and economic support through cash transfers conditional upon TB screening in household contacts, adhering to TB treatment/chemoprophylaxis and engaging with social support. Data were collected to assess TB-affected household costs. Patient interviews were conducted at treatment initiation and then monthly for 6 months.From February 2014 to June 2015, 312 households were recruited, of which 135 were randomised to receive the intervention. Cash transfer total value averaged US$173 (3.5% of TB-affected households' average annual income) and mitigated 20% of households' TB-related costs. Households randomised to receive the intervention were less likely to incur catastrophic costs (30% (95% CI 22-38%) versus 42% (95% CI 34-51%)). The mitigation impact was higher among poorer households.The TB-specific socioeconomic intervention reduced catastrophic costs and was accessible to poorer households. Socioeconomic support and mitigating catastrophic costs are integral to the End TB strategy, and our findings inform implementation of these new policies.

Impact of Infection Control Measures to Control an Outbreak of Multidrug-Resistant Tuberculosis in a Human Immunodeficiency Virus Ward, Peru.

Multidrug-resistant tuberculosis (MDRTB) rates in a human immunodeficiency virus (HIV) care facility increased by the year 2000-56% of TB cases, eight times the national MDRTB rate. We reported the effect of tuberculosis infection control measures that were introduced in 2001 and that consisted of 1) building a respiratory isolation ward with mechanical ventilation, 2) triage segregation of patients, 3) relocation of waiting room to outdoors, 4) rapid sputum smear microscopy, and 5) culture/drug-susceptibility testing with the microscopic-observation drug-susceptibility assay. Records pertaining to patients attending the study site between 1997 and 2004 were reviewed. Six hundred and fifty five HIV/TB-coinfected patients (mean age 33 years, 79% male) who attended the service during the study period were included. After the intervention, MDRTB rates declined to 20% of TB cases by the year 2004 (P = 0.01). Extremely limited access to antiretroviral therapy and specific MDRTB therapy did not change during this period, and concurrently, national MDRTB prevalence increased, implying that the infection control measures caused the fall in MDRTB rates. The infection control measures were estimated to have cost US$91,031 while preventing 97 MDRTB cases, potentially saving US$1,430,026. Thus, this intervention significantly reduced MDRTB within an HIV care facility in this resource-constrained setting and should be cost-effective.

Interconnected microbiomes and resistomes in low-income human habitats.

Antibiotic-resistant infections annually claim hundreds of thousands of lives worldwide. This problem is exacerbated by exchange of resistance genes between pathogens and benign microbes from diverse habitats. Mapping resistance gene dissemination between humans and their environment is a public health priority. Here we characterized the bacterial community structure and resistance exchange networks of hundreds of interconnected human faecal and environmental samples from two low-income Latin American communities. We found that resistomes across habitats are generally structured by bacterial phylogeny along ecological gradients, but identified key resistance genes that cross habitat boundaries and determined their association with mobile genetic elements. We also assessed the effectiveness of widely used excreta management strategies in reducing faecal bacteria and resistance genes in these settings representative of low- and middle-income countries. Our results lay the foundation for quantitative risk assessment and surveillance of resistance gene dissemination across interconnected habitats in settings representing over two-thirds of the world's population.