High Burden Countries Research Articles

Time to Treatment and Risk Factors for Unsuccessful Treatment Outcomes among People Who Started Second-Line Treatment for Rifampicin-Resistant or Multi-Drug-Resistant Tuberculosis in the Kyrgyz Republic, 2021.

The Kyrgyz Republic is a high-burden country for rifampicin resistant/multi-drug resistant tuberculosis (RR/MDR-TB). TB control efforts rely on early diagnosis and initiation of people on effective regimens. We studied the interval from diagnosis of RR-TB to starting treatment and risk factors for unsuccessful outcomes among people who started RR/MDR-TB treatment in 2021. We conducted a cohort study using country-wide programme data and used binomial regression to determine associations between unsuccessful outcomes and predictor variables. Of the 535 people included in the study, three-quarters were in the age category 18-59 years, and 68% had past history of TB. The median (IQR) time from onset of TB symptoms to diagnosis was 30 (11-62) days, 1 (0-4) days from diagnosis to starting treatment, and 35 (24-65) days from starting treatment to receipt of second-line drug susceptibility test (SL-DST) results. Overall, 136 (25%) had unsuccessful outcomes. Risk factors for unsuccessful outcomes were being homeless, fluroquinolone resistance, having unknown HIV status, past TB treatment, male gender and being unemployed. Treatment outcomes and the interval from diagnosis to starting treatment were commendable. Further reductions in unsuccessful outcomes by be achieved through ensuring timely diagnosis and access to SL-DSTs and by reducing the proportion of people who are lost to follow-up.

Generic Implementation Framework approach for public private mix in Tuberculosis control at a private hospital in Gresik, East Java, Indonesia

Background and purpose: Tuberculosis continues to be a concern at the global level. Indonesia is a high-burden country that keeps efforts through TB control programs by implementing a private-public mix (PPM) strategy. This study aims to analyze the implementation of PPM in a private hospital using the Generic Implementation Framework approach. Methods: This study conducted a mixed method approach including quantitative and qualitative analysis of data with explanatory sequential design. The analyzed variables were the assessment elements used in determining hospital accreditation, variables to get an overview of PPM, and achievement of indicators. Quantitative data were analyzed descriptively, while the qualitative with thematic analysis. Results: The quality of TB control at the hospital was under the accreditation standards. There was an increase in the number of patients treated but uptrend in the number of loss to follow-up patients in the last three years. The success rate of treatment in 2021 has not yet achieved as it was influenced by patients who were lost to follow-up and treatment failure. Supporting factors for the PPM implementation were the script of cooperation, commitment, cooperation, communication, mutual trust, maintained service quality, inter-dependence, and mutual benefit as inhibiting factors related to the management of treatment adherence. Conclusion: The achievement of program indicators has yet to meet the target. Therefore, it is necessary to evaluate regulations, standard operating procedures, and cooperation scripts to reach the standard.

Analytical performances of the Xpert MTB/RIF assay using stool specimens to improve the diagnosis of pulmonary tuberculosis in Burkina Faso, a tuberculosis endemic country.

Timely diagnosis of Pulmonary Tuberculosis (PTB) is associated with good prognosis, but remains difficult in primary healthcare facilities and particularly in children and patients living with HIV. The aim of this study was to compare the GeneXpert ® MTB/RIF assay (Xpert) performed using a stool sample (3-5 g) and using the first Respiratory Tract Sample (RTS; i.e., sputum, bronchoalveolar or gastric aspirate; as normally done) concomitantly collected from 119 patients with suspected PTB to improve PTB diagnosis in Burkina Faso, a high tuberculosis burden country with limited resources. Overall, microbiological, microscopic and molecular analysis of the 119 first RTS and 119 stool specimens led to Mycobacterium tuberculosis complex detection in 28 patients (23 positive RTS cultures and 5 negative RTS cultures-RTS Xpert positive). When using the 28 clinical confirmed cases as reference standard, the sensitivities of the stool-based and RTS-based Xpert assays were not different (24/28, 85.7%, versus 26/28, 92.86%; p > 0.30), and 22 results were fully concordant. Considering the first RTS culture as the gold standard, the sensitivities of the stool-based and RTS-based Xpert assays to detect PTB in patients with positive RTS culture were 100% (23/23) and 91.3% (21/23), respectively (p >0.05). The stool-based Xpert assay specificity for excluding PTB was 99% (95/96) (compared with 95%, 91/96, when using RTS) and its negative and positive predictive values were 100% (95/95) and 96% (23/24), respectively. Compared with the 23 positive RTS cultures, the incremental yield rates of the RTS-based and stool-based Xpert assays were 4.2% (5/119) and 0.84% (1/119), respectively. Overall, our findings support using the stool-based Xpert assay as an alternative method for earlier PTB diagnosis, when RTS are difficult to obtain.

Impact of malaria diagnostic choice on monitoring of Plasmodium falciparum prevalence estimates in the Democratic Republic of the Congo and relevance to control programs in high-burden countries.

Malaria programs rely upon a variety of diagnostic assays, including rapid diagnostic tests (RDTs), microscopy, polymerase chain reaction (PCR), and bead-based immunoassays (BBA), to monitor malaria prevalence and support control and elimination efforts. Data comparing these assays are limited, especially from high-burden countries like the Democratic Republic of the Congo (DRC). Using cross-sectional and routine data, we compared diagnostic performance and Plasmodium falciparum prevalence estimates across health areas of varying transmission intensity to illustrate the relevance of assay performance to malaria control programs. Data and samples were collected between March-June 2018 during a cross-sectional household survey across three health areas with low, moderate, and high transmission intensities within Kinshasa Province, DRC. Samples from 1,431 participants were evaluated using RDT, microscopy, PCR, and BBA. P. falciparum parasite prevalence varied between diagnostic methods across all health areas, with the highest prevalence estimates observed in Bu (57.4-72.4% across assays), followed by Kimpoko (32.6-53.2%), and Voix du Peuple (3.1-8.4%). Using latent class analysis to compare these diagnostic methods against an "alloyed gold standard," the most sensitive diagnostic method was BBA in Bu (high prevalence) and Voix du Peuple (low prevalence), while PCR diagnosis was most sensitive in Kimpoko (moderate prevalence). RDTs were consistently the most specific diagnostic method in all health areas. Among 9.0 million people residing in Kinshasa Province in 2018, the estimated P. falciparum prevalence by microscopy, PCR, and BBA were nearly double that of RDT. Comparison of malaria RDT, microscopy, PCR, and BBA results confirmed differences in sensitivity and specificity that varied by endemicity, with PCR and BBA performing best for detecting any P. falciparum infection. Prevalence estimates varied widely depending on assay type for parasite detection. Inherent differences in assay performance should be carefully considered when using community survey and surveillance data to guide policy decisions.

Pragmatic cluster-randomized trial of home-based preventive treatment for TB in Ethiopia and South Africa (CHIP-TB)

BackgroundEach year, 1 million children develop TB resulting in over 200,000 child deaths. TB preventive treatment (TPT) is highly effective in preventing TB but remains poorly implemented for household child contacts. Home-based child contact management and TPT services may improve access to care. In this study, we aim to evaluate the effectiveness and cost-effectiveness of home-based contact management with TPT initiation in two TB high-burden African countries, Ethiopia and South Africa.MethodsThis pragmatic cluster randomized trial compares home-based versus facility-based care delivery models for contact management. Thirty-six clinics with decentralized TB services (18 in Ethiopia and 18 in South Africa) were randomized in a 1:1 ratio to conduct either home-based or facility-based contact management. The study will attempt to enroll all eligible close child contacts of infectious drug-sensitive TB index patients diagnosed and treated for TB by one of the study clinics. Child TB contact management, including contact tracing, child evaluation, and TPT initiation and follow-up, will take place in the child’s home for the intervention arm and at the clinic for the control arm. The primary outcome is the cluster-level ratio of the number of household child contacts less than 15 years of age in Ethiopia and less than 5 years of age in South Africa initiated on TPT per index patient, comparing the intervention to the control arm. Secondary outcomes include child contact identification and the TB prevention continuum of care. Other implementation outcomes include acceptability, feasibility, fidelity, cost, and cost-effectiveness of the intervention.DiscussionThis implementation research trial will determine whether home-based contact management identifies and initiates more household child contacts on TPT than facility-based contact management.Trial registrationNCT04369326. Registered on April 30, 2020.

Clinical utilization of multiple antibodies of Mycobacterium tuberculosis for serodiagnosis evaluation of tuberculosis: a retrospective observational cohort study

Objectives We aimed to investigate clinical uncertainties by characterizing the accuracy and utility of commercially available antibodies of Mycobacterium tuberculosis in the diagnostic assessment of suspected tuberculosis in high-burden countries. Methods We conducted a retrospective, descriptive, cohort study among participants aged ≥ 18 years with suspected tuberculosis in Nanning, Guangxi, and China. Participants were tested for M. tuberculosis infection using commercially available antibodies against Mycobacterum tuberculosis. Specificity, sensitivity, negative and positive predictive values, and negative and positive likelihood ratios of the tests were determined. Sputum specimens and bronchoalveolar lavage fluid were sent for mycobacterial culture, Xpert MTB/RIF assay, and cell-free M. tuberculosis DNA or RNA assay. Blood samples were used for IGRAs, T-cell counts (CD3 + CD4+ and CD3 + CD8+), and antibodies to tuberculosis test. Results Of the 1857 participants enrolled in this study, 1772 were included in the analyses, among which, 1311 were diagnosed with active tuberculosis. The specificity of antibody against 16kD for active tuberculosis was 92.7% (95% confidence interval [CI]: 89.3–95.4) with a positive likelihood ratio for active tuberculosis cases of 3.1 (95% CI: 2.1–4.7), which was higher than that of antibody to Rv1636 (90.5% [95% CI: 86.6–93.5]), antibody to 38kD (89.5% [95% CI: 85.5–92.7]), antibody against CFP-10 (82.6% [95% CI: 77.9–86.7]), and antibody against LAM (79.3% [95% CI: 74.3–83.7]). Sensitivity ranged from 15.8% (95% CI: 13.9–17.9) for antibody against Rv1636 to 32.9% (95% CI: 30.4–35.6) for antibody to LAM. Conclusions Commercially available antibodies against to Mycobacterium tuberculosis do not have sufficient sensitivity for the diagnostic evaluation of active tuberculosis. However, antibody against Rv1636 and 16kD may have sufficiently high specificities, high positive likelihood ratios, and correspondingly high positive predictive values to facilitate the rule-in of active tuberculosis.

Hepatitis B viral replication markers and hepatic fibrosis in untreated chronic hepatitis B virus infection with and without HIV coinfection in Zambia.

To inform novel therapies, a more nuanced understanding of HIV's impact on hepatitis B virus (HBV) natural history is needed, particularly in high burden countries. In Lusaka, Zambia, we compared prospectively recruited adults (18+ years) with chronic HBV infection, with and without HIV. We excluded those with prior antiviral treatment experience or HBV diagnosis due to clinical suspicion (rather than routine testing). We assessed HBV DNA levels, hepatitis B e antigen (HBeAg), CD4 + (if HIV coinfection), and liver disease (transient elastography, serum alanine aminotransferase). In multivariable analyses, we evaluated the association of HIV overall and by level of CD4 + count on these markers. Among 713 adults analyzed, median age was 33 years, 63% were male, and 433 had HBV/HIV coinfection. Median CD4 + count was 200 cells/μl. HBV DNA was greater than 2000 IU/ml for 311 (51.0%) and 227 (32.5%) were HBeAg-positive. 15.5% had advanced fibrosis or cirrhosis. HIV coinfection was associated with five-fold increased HBV DNA levels [adjusted geometric mean ratio, 5.78; 95% confidence interval (CI), 2.29-14.62] and two times the odds of HBeAg-positivity (adjusted odds ratio, 2.54; 95% CI, 1.59-4.08). These associations were significant only at CD4 + counts 100-350 and <100 cells/μl. HIV was not associated with markers of fibrosis or ALT. HIV's impact on HBV natural history likely depends on the degree and duration of immune suppression. There is strong rationale to monitor HBV DNA in people with HBV/HIV coinfection and immune suppression. A better understanding is needed of mechanisms of increased liver-related mortality in people with HBV/HIV coinfection.

Health effects of routine measles vaccination and supplementary immunisation activities in 14 high-burden countries: a Dynamic Measles Immunization Calculation Engine (DynaMICE) modelling study

WHO recommends at least 95% population coverage with two doses of measles-containing vaccine (MCV). Most countries worldwide use routine services to offer a first dose of measles-containing vaccine (MCV1) and later, a second dose of measles-containing vaccine (MCV2). Many countries worldwide conduct supplementary immunisation activities (SIAs), offering vaccination to all people in a specific age range irrespective of previous vaccination history. We aimed to estimate the relative effects of each dose and delivery route in 14 countries with high measles burden. We used an age-structured compartmental dynamic model, the Dynamic Measles Immunization Calculation Engine (DynaMICE), to assess the effects of different vaccination strategies on measles susceptibility and burden during 2000-20 in 14 countries with high measles incidence (containing 53% of the global birth cohort and 78% of the global measles burden). Country-specific routine MCV1 and MCV2 coverage data during 1980-2020 were obtained from the WHO and UNICEF Estimates of National Immunization Coverage database for all modelled countries and SIA data were obtained from the WHO summary of measles and rubella SIAs. We estimated the incremental health effects of different vaccination strategies using prevented cases of measles and deaths from measles and their efficiency using the incremental number needed to vaccinate (NNV) to prevent an additional measles case. Compared with no vaccination, MCV1 implementation was estimated to have prevented 824 million cases of measles and 9·6 million deaths from measles, with a median NNV of 1·41 (IQR 1·35-1·44). Adding routine MCV2 to MCV1 was estimated to have prevented 108 million cases and 404 270 deaths, whereas adding SIAs to MCV1 was estimated to have prevented 256 million cases and 4·4 million deaths. Despite larger incremental effects, adding SIAs to MCV1 (median incremental NNV 6·02, 5·30-7·68) showed reduced efficiency compared with adding routine MCV2 (5·41, 4·76-6·11). Vaccination strategies, including non-selective SIAs, reach a greater proportion of children who are unvaccinated and reduce measles burden more than MCV2 alone, but efficiency is lower because of the wide age range targeted by SIAs. This analysis provides information to help improve the health effects and efficiency of measles vaccination strategies. The interplay between MCV1, MCV2, and SIAs should be considered when planning future measles vaccination strategies. Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

Retrospective Study on the Incidence of Tuberculosis Cases in Pakistan

Tuberculosis (TB) is a serious infection or disease that directly affects the lungs. Pakistan stands 5th ranks amongst the high burden countries in the world. This study addresses the relationships between different tuberculosis cases in the province of Pakistan. The study is used to find which province reported high tuberculosis cases like (bacteriologically confirmed, clinically diagnosed, extra pulmonary and retreated tuberculosis). The main objective of this study is to know which tuberculosis case has significant effect among the provinces. For this purpose, we find the mean difference among the province of Pakistan with concern to tuberculosis cases in this study. The secondary data is used in this study. Further we find the correlation between tuberculosis cases and then used factor analysis. The dataset is taken by the website of the national TB data and Pakistan bureau of statistics. The dataset includes four different cases of tuberculosis (bacteriologically confirmed, clinically diagnosed, extra pulmonary and retreated tuberculosis) in provinces of Pakistan during the period of 2019. For achieving the objectives of the study, different techniques are used such as graphical representation, descriptive statistics, two-way ANOVA, LSD Test, correlation matrix, and factor analysis. The study shows highly significant results and concluded that the highest numbers of cases and deaths are reported in Punjab. Correlation matrix shows strong positive correlation between the four cases of tuberculosis. From factor analysis, there is only one factor is extracted that explains 82.872% of the total variation and all the cases have strong correlation with the factor.

Impact of the COVID-19 Pandemic on tuberculosis management in India: A Brief Overview

Chronicles suggests that emerging and re-emerging viral infections disrupting the normal lifestyle of humankind, whether in the form of HIV, Ebola, Influenza, Nepah, or the current SARS-CoV-2 pandemic. Such viral infections disrupt the healthcare system along with the prevention and control of epidemics and pandemics, resulting in an increased burden of such diseases in the post-pandemic period. Tuberculosis (TB) routine services are interfered with by severe lockdowns due to the new COVID-19 virus. This article tried to measure the long-term epidemiological effects of such interruptions on TB prevalence in high-burden countries. The participating facilities performed a comprehensive review based on modifications to the care of TB patients during the COVID-19 pandemic. Retrospectively, clinical factors and household contact information were collected from a literature survey. Researchers looked at numerous strategies over the following five years to see whether they might lessen the effects on TB incidence and death. Present comprehensive literature was collected and analyzed using suitable keywords such as "COVID-19," "Pandemics," "Tuberculosis," and "India" during the current COVID-19 pandemic to investigate the influence of COVID-19 on tuberculosis management. The present article looks at the effects of the breaks in the delivery of TB care in hospital and primary care settings. Lockdown, social isolation, measures to prevent viral transmission, and public health guidelines impacted tuberculosis care. The present study revealed that the COVID-19 pandemic has adversely affected numerous TB prevention, monitoring, and treatment programs. Still, these adverse effects are diminished by the prompt restoration of TB services and the application of particular therapies as soon as restrictions are lifted.

Recovery of Routine Immunisation: Mapping External Financing Opportunities for Reaching Zero-Dose Children.

The COVID-19 pandemic has precipitated large declines in childhood vaccination coverage and, consequently, substantial increases in the number of zero-dose children. To effectively respond to these declines, it is necessary to direct resources for recovery. We mapped active external financing for immunisation and primary healthcare in 20 countries with the highest numbers of zero-dose children to promote transparency and donor coordination. We found that countries have disparate access to external financing, with the two upper-middle-income countries (Brazil and Mexico) only having access to loans from the International Bank for Reconstruction and Development. Domestic resource mobilization is, therefore, key in these two countries, although fiscal space is likely constrained. Four additional countries (Angola, Indonesia, Philippines, and Vietnam) do not have allocations from Gavi, the Vaccine Alliance for Health Systems Strengthening, or Equity Accelerator Funding, but are eligible for support under Gavi's Middle-Income Countries Approach. Our methods, which focus on current donor financing, are novel and reveal substantial variations in access to external financing to support immunisation in high-burden countries. The available data differ considerably across financing mechanisms, making it difficult to synthesise the results across funding sources.

Forecasting Incidence Prevalence of Tuberculosis in Azad Jammu &amp; Kashmir: A Five-Year Retrospective Study

Background: Tuberculosis is one of the critical public health issue in Pakistan, according to report of WHO (2018), it holds 5th place among the TB high burden countries and estimated to be on fourth position for MDR prevalence. Currently, Pakistan is sharing 61% of case burden of TB in EMRO region. Methods: Polynomial regression model was used to predict the tuberculosis incidence prevalence in AJ&amp;K for the year 2019. Estimation based on tuberculosis data (2014-2018) analyzed for the incidence prevalence of tuberculosis in AJ&amp;K for 2019. Results: Tuberculosis incidence prevalence for 2018 was obtained 118/100000. The actual data of 2018 reported shows that averagely incidence prevalence of TB remains 124/100000 with minor difference from the predicted value of 2018. The data analysis from 2014 to 2018; predicted that average 130/100000 cases will be reported in 2019. Conclusion: This shows that AJ&amp;K is far from the target (270/100000) recognized by WHO. If one TB case produces 10 cases in community annually, then in coming years, there will be adversity of TB cases in the AJ&amp;K. It is suggested to WHO to revise its target.

Multi-drug resistant and rifampin-resistant tuberculosis in transplant recipients.

Management of multidrug-resistant (MDR) and rifampin-resistant (RR) tuberculosis is challenging. Data on transplant recipients is limited. We reviewed published literature to examine treatment choices, outcomes, and adverse effects from MDR-TB/RR-TB treatment in transplant recipients. Multiple databases from inception to 12/2022 were reviewed using the keywords "drug-resistant TB" or "drug-resistant tuberculosis" or "multidrug-resistant TB" or "multidrug-resistant tuberculosis". MDR-TB was defined as resistance to isoniazid (H) and rifampin (R), and RR if resistant to rifampin alone. Cases without patient-level data and reports which did not describe treatment and/or outcomes for MDR-TB were excluded. A total of 12 patients (10 solid organ transplants and two hematopoietic cell transplants) were included. Of these, 11 were MDR-TB and one was RR-TB. Seven recipients were male. The median age was 41.5 (range 16-60) years. Pre-transplant evaluation for the majority (8/12, 66.7%) did not reveal a prior history of TB or TB treatment, but 9/12 were from TB intermediate or high-burden countries. Seven patients were initially treated with the quadruple first-line anti-TB regimen. Those who had early RR confirmation (5/12) via Xpert MTB/RIF assay were initiated on alternative therapies. Final regimens were individualized based on susceptibility profiles and tolerability. Adverse events were reported in seven recipients, including acute kidney injury (n = 3), cytopenias (n = 3), and jaundice (n = 2). Four recipients died, with two deaths attributable to TB. The remaining eight patients who survived had functioning allografts at the last follow-up. MDR-TB treatment in transplant recipients is associated with many complications. Xpert MTB/RIF detected RR early and guided early empiric therapy.

Insight into Population Structure and Drug Resistance of Pediatric Tuberculosis Strains from China and Russia Gained through Whole-Genome Sequencing.

This study aimed to determine phenotypic and genotypic drug resistance patterns of Mycobacterium tuberculosis strains from children with tuberculosis (TB) in China and Russia, two high-burden countries for multi/extensively-drug resistant (MDR/XDR) TB. Whole-genome sequencing data of M. tuberculosis isolates from China (n = 137) and Russia (n = 60) were analyzed for phylogenetic markers and drug-resistance mutations, followed by comparison with phenotypic susceptibility data. The Beijing genotype was detected in 126 Chinese and 50 Russian isolates. The Euro-American lineage was detected in 10 Russian and 11 Chinese isolates. In the Russian collection, the Beijing genotype and Beijing B0/W148-cluster were dominated by MDR strains (68% and 94%, respectively). Ninety percent of B0/W148 strains were phenotypically pre-XDR. In the Chinese collection, neither of the Beijing sublineages was associated with MDR/pre-XDR status. MDR was mostly caused by low fitness cost mutations (rpoB S450L, katG S315T, rpsL K43R). Chinese rifampicin-resistant strains demonstrated a higher diversity of resistance mutations than Russian isolates (p = 0.003). The rifampicin and isoniazid resistance compensatory mutations were detected in some MDR strains, but they were not widespread. The molecular mechanisms of M. tuberculosis adaptation to anti-TB treatment are not unique to the pediatric strains, but they reflect the general situation with TB in Russia and China.

A mixed methods study on men's and women's tuberculosis care journeys in Lusaka, Zambia-Implications for gender-tailored tuberculosis health promotion and case finding strategies.

Men and women with undiagnosed tuberculosis (TB) in high burden countries may have differential factors influencing their healthcare seeking behaviors and access to TB services, which can result in delayed diagnoses and increase TB-related morbidity and mortality. A convergent, parallel, mixed-methods study design was used to explore and evaluate TB care engagement among adults (≥18 years) with newly diagnosed, microbiologically-confirmed TB attending three public health facilities in Lusaka, Zambia. Quantitative structured surveys characterized the TB care pathway (time to initial care-seeking, diagnosis, and treatment initiation) and collected information on factors influencing care engagement. Multinomial multivariable logistic regression was used to determine predicted probabilities of TB health-seeking behaviors and determinants of care engagement. Qualitative in-depth interviews (IDIs; n = 20) were conducted and analyzed using a hybrid approach to identify barriers and facilitators to TB care engagement by gender. Overall, 400 TB patients completed a structured survey, of which 275 (68.8%) and 125 (31.3%) were men and women, respectively. Men were more likely to be unmarried (39.3% and 27.2%), have a higher median daily income (50 and 30 Zambian Kwacha [ZMW]), alcohol use disorder (70.9% [AUDIT-C score ≥4] and 31.2% [AUDIT-C score ≥3]), and a history of smoking (63.3% and 8.8%), while women were more likely to be religious (96.8% and 70.8%) and living with HIV (70.4% and 36.0%). After adjusting for potential confounders, the probability of delayed health-seeking ≥4 weeks after symptom onset did not differ significantly by gender (44.0% and 36.2%, p = 0.14). While the top reasons for delayed healthcare-seeking were largely similar by gender, men were more likely to report initially perceiving their symptoms as not being serious (94.8% and 78.7%, p = 0.032), while women were more likely to report not knowing the symptoms of TB before their diagnosis (89.5% and 74.4%; p = 0.007) and having a prior bad healthcare experience (26.4% and 9.9%; p = 0.036). Notably, women had a higher probability of receiving TB diagnosis ≥2 weeks after initial healthcare seeking (56.5% and 41.0%, p = 0.007). While men and women reported similar acceptability of health-information sources, they emphasized different trusted messengers. Also, men had a higher adjusted probability of stating that no one influenced their health-related decision making (37.9% and 28.3%, p = 0.001). In IDIs, men recommended TB testing sites at convenient community locations, while women endorsed an incentivized, peer-based, case-finding approach. Sensitization and TB testing strategies at bars and churches were highlighted as promising approaches to reach men and women, respectively. This mixed-methods study found important differences between men and women with TB in Zambia. These differences suggest the need for gender-tailored TB health promotion, including addressing harmful alcohol use and smoking among men, and sensitizing HCWs to prolonged delays in TB diagnosis among women, and also using gender-specific approaches as part of community-based, active case-finding strategies to improve TB diagnosis in high burden settings.

Case Report: Subfertility and Pregnancy Loss due to Genital Tuberculosis

Tuberculosis (TB) is a disease that primarily affects low and middle income countries (LMICs) but is becoming more relevant in Western countries due to increasing migration from high TB burden countries. It is especially difficult to detect in women with fertility issues as it mimics other more common causes. Delayed diagnosis of TB can result in fallopian tube and endometrial pathology leading to subfertility and pregnancy loss. This case report describes a 34-year-old woman from Ivory Coast who was diagnosed with intrauterine tuberculosis after hysteroscopic evacuation of suspected retained placental tissue following an immature delivery. The patient had a complicated fertility history, including pelvic inflammatory disease and IVF/ICSI procedures, before becoming pregnant at the age of 38. She delivered prematurely at 22 weeks with a retained placenta. A diagnosis of TB was confirmed after pathology revealed granulomatous inflammation, without signs of placental tissue, and further testing confirmed rifampicin-resistant TB. The patient underwent a 15-month course of multi-drug-resistant TB treatment, which postponed her pregnancy wish. The case highlights the challenge of diagnosing genital TB in the female genital tract during subfertility investigations and after a complicated pregnancy in a woman without a history of or symptoms of TB. It underscores the importance of considering TB in the differential diagnosis of subfertility. Screening should be considered in women originating from high endemic countries with unexplained fertility loss and during first trimester screening.

Effect of Stenotrophomonas maltophilia on Tuberculosis.

Tuberculosis (TB) is an important infectious disease suffered by many countries, including China. In this stage, accurate diagnosis and treatment are key measures for the prevention and control of TB. Stenotrophomonas maltophilia is a global emerging Gram-negative, multidrug-resistant (MDR) organism characterized by its high contribution to the increase in crude mortality rates. By single cell preparation and strain identification, we isolated S. maltophilia from stored cultures of Mycobacterium tuberculosis (Mtb). We found that S. maltophilia could not be removed from sputum by alkali treatment or inhibited by antibiotic mixture added to MGIT 960 indicator tubes. When co-cultured with Mtb on a Löwenstein-Jensen (L-J) slant, it could inhibit the growth of Mtb and liquefy the medium. More seriously, it was resistant to 10 of the 12 anti-TB drugs, including isoniazid and rifampin, and made the mixed samples display multidrug-resistant Mtb (MDR-TB) results in the drug sensitivity test, which might change a treatment regimen and increase disease burden. Following, we conducted a small-scale surveillance which showed that the isolation rate of S. maltophilia in TB patients was 6.74%, but these patients had no special characteristics and the presence of S. maltophilia was hidden. The effect of S. maltophilus on TB and its mechanism are unclear and require more attention. IMPORTANCE China is a high-burden country for tuberculosis (TB), multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB), and HIV-associated TB. Increasing the positive rate of culture and the accuracy of antibiotic susceptibility testing (AST) are important for diagnosis, treatment, and control of TB. In our study, we found that the isolation rate of Stenotrophomonas maltophilia in TB patients was not neglectable and that this bacterium affects the isolation and AST results of TB. Due to a lack of relevant research, the impact of S. maltophilia on the course and outcome of TB is unclear. However, the characteristics of S. maltophilia that increase disease mortality require attention. Therefore, in the clinical testing of TB, in addition to mycobacteria, it is recommended to increase the detection of co-infected bacteria and improve the awareness of TB clinicians of these bacteria.

Comparing cross-sectional andlongitudinal approaches to tuberculosis patient cost surveys using Nepalese data.

The World Health Organization has supported the development of national tuberculosis (TB) patient cost surveys to quantify the socio-economic impact of TB in high-burden countries. However, methodological differences in the study design (e.g. cross-sectional vs longitudinal) can generate different estimates making the design and impact evaluation of socio-economic protection strategies difficult. The objective of the study was to compare the socio-economic impacts of TB estimated by applying cross-sectional or longitudinal data collections in Nepal. We analysed the data from a longitudinal costing survey (patients interviewed at three time points) conducted between April 2018 and October 2019. We calculated both mean and median costs from patients interviewed during the intensive (cross-sectional 1) and continuation (cross-sectional 2) phases of treatment. We then compared costs, the prevalence of catastrophic costs and the socio-economic impact of TB generated by each approach. There were significant differences in the costs and social impacts calculated by each approach. The median total cost (intensive plus continuation phases) was significantly higher for the longitudinal compared with cross-sectional 2 (US$119.42 vs 91.63, P < 0.001). The prevalence of food insecurity, social exclusion and patients feeling poorer or much poorer were all significantly higher by applying a longitudinal approach. In conclusion, the longitudinal design captured important aspects of costs and socio-economic impacts, which were missed by applying a cross-sectional approach. If a cross-sectional approach is applied due to resource constraints, our data suggest that the start of the continuation phase is the optimal timing for a single interview. Further research to optimize methodologies to report patient-incurred expenditure during TB diagnosis and treatment is needed.

Taking on Typhoid: Eliminating Typhoid Fever as a Global Health Problem.

Typhoid fever is a significant global health problem that impacts people living in areas without access to clean water and sanitation. However, collaborative international partnerships and new research have improved both knowledge of the burden in countries with endemic disease and the tools for improved surveillance, including environmental surveillance. Two typhoid conjugate vaccines (TCVs) have achieved World Health Organization prequalification, with several more in the development pipeline. Despite hurdles posed by the coronavirus disease 2019 pandemic, multiple TCV efficacy trials have been conducted in high-burden countries, and data indicate that TCVs provide a high degree of protection from typhoid fever, are safe to use in young children, provide lasting protection, and have the potential to combat typhoid antimicrobial resistance. Now is the time to double down on typhoid control and elimination by sustaining progress made through water, sanitation, and hygiene improvements and accelerating TCV introduction in high-burden locations.

EPH189 Assessment of Burden of COVID-19 Infection and the Dynamics in African Union Member States

This study assessed the real-world burden of COVID-19 infection in African Union (AU) member states during the first 12 months of the pandemic using selected epidemiological measures. Data were sourced from the African CDC and Our World in Data,for time period spanning February 2020 to January 2021. AU member states were classified into low, medium and high burden based on COVID-19 morbidity. We conducted descriptive and inferential analyses of the following epidemiological measures: morbidity and mortality rates (MMRs), case fatality rate (CFR), and case ratios. A total of 3.2 million COVID-19 cases were reported during the first 12 months, with 2.6 million recoveries, 536,784 cases remaining active, and 77, 486 deaths. Most countries in AU experienced low burden of COVID-19 (49.1%, n=26) compared to 28.3% (n=15) with medium and 22.6% (n=12) with high burden of the disease. South Africa recorded the highest number of cases (1.31 million) followed by Morocco with 457,625 and Tunisia with 175,065 cases. Correspondently, death tolls for these countries were 36,467, 7,888 and 5,528 deaths, respectively. Of the total COVID-19 tests performed (83.8 million) during the first 12 months, 62.43% were from high burden countries. The least testing occurred in the medium burden (18.42%) countries. The overall CFR of AU was 2.21%. Morbidity rate of 327.52/105 population and mortality rate of 5.96/105 population were recorded during the period with significant (p<0.0001) variations across burden levels and regions. Continental morbidity and mortality rates of 17,359/105 population and 315.933/105 population were recorded with significant correlation (r=0.863, p<0.0001) between them and variations across selected epidemiological measures by COVID-19 burden levels. Understanding the true burden of the disease in AU countries is important for establishing the impact of the pandemic in the African continent and for intervention planning and deployment of resources including vaccines.