Sudan is endemic for multiple neglected tropical diseases, including trachoma, onchocerciasis (OV), lymphatic filariasis (LF), and schistosomiasis (SCH). In 2019, dried blood spot samples were collected for a baseline trachoma serosurvey in three localities (El Seraif, Kotom, and Saraf Omrah) in North Darfur State. None were classified previously as OV- or LF-endemic, although low levels of SCH had been identified in all three. Approximately 30 households from 25 communities in each locality were selected by multistage cluster random sampling. Collections of DBSs were analyzed by multiplex bead assay for antibodies to multiple pathogens. This paper presents data on OV (Ov16), LF (Wb123, Bm14, Bm33), and SCH (soluble egg antigen [SEA], Sm25) antibodies among 8,322 individuals from 2,119 households. The survey-adjusted seroprevalence estimates for Ov16 were <0.3% in all localities. Lymphatic filariasis-antigen seroprevalences were discordant. Seroprevalence estimates ranged from 4.6-6.0% (Wb123), 0.99-1.4% (Bm14), and 29.2-33.3% (Bm33). Schistosomiasis seroprevalence estimates among school-aged children ranged from 2.7-8.0% (SEA) and 10.9-15.6% (Sm25). Ov16 seropositivity was low and supported the localities' classification as nonendemic. The results suggested LF exposure, but discordance between antigens, challenges defining seropositivity thresholds, and the absence of programmatic guidance based on antibody serology alone for Wuchereria bancrofti indicate a need for remapping surveys to confirm transmission. Schistosomiasis antibody levels were high enough to warrant further mapping to guide treatment decisions. The lack of gold standards limited interpretation of results, particularly for LF, but in resource-challenged areas, integrated serological surveillance offers the possibility of efficient monitoring of exposure to multiple diseases.

BACKGROUND: Invasive meningococcal isolates in South Africa have in previous years (<2008) been characterized by serogroup B, C, W and Y lineages over time, with penicillin intermediate resistance (peni) at 6%. We describe the population structure and genomic markers of peni among invasive meningococcal isolates in South Africa, 2016-2021. METHODS: Meningococcal isolates were collected through national, laboratory-based invasive meningococcal disease (IMD) surveillance. Phenotypic antimicrobial susceptibility testing and whole-genome sequencing were performed, and the mechanism of reduced penicillin susceptibility was assessed in silico. RESULTS: Of 585 IMD cases reported during the study period, culture and PCR-based capsular group was determined for 477/585 (82%); and 241/477 (51%) were sequenced. Predominant serogroups included NmB (210/477; 44%), NmW (116/477; 24%), NmY (96/477; 20%) and NmC (48/477; 10%). Predominant clonal complexes (CC) were CC41/44 in NmB (27/113; 24%), CC11 in NmW (46/56; 82%), CC167 in NmY (23/44; 53%), and CC865 in NmC (9/24; 38%). Peni was detected in 16% (42/262) of isolates, and was due to the presence of a penA mosaic, with the majority harboring penA7, penA9 or penA14. CONCLUSION: IMD lineages circulating in South Africa were consistent with those circulating prior to 2008, however peni was higher than previously reported, and occurred in a variety of lineages.

Social network strategy (SNS) testing uses network connections to refer individuals at high risk to HIV testing services (HTS). In Tanzania, SNS testing is offered in communities and health facilities. In communities, SNS testing targets key and vulnerable populations (KVP), while in health facilities it complements index testing by reaching unelicited index contacts. Routine data were used to assess performance and trends over time in PEPFAR-supported sites between October 2021 and March 2023. Key indicators included SNS social contacts tested, and new HIV-positives individuals identified. Descriptive and statistical analysis were conducted. Univariable and multivariable analysis were applied, and variables with P-values <0.2 at univariable analysis were considered for multivariable analysis. Overall, 121,739 SNS contacts were tested, and 7731 (6.4%) previously undiagnosed individuals living with HIV were identified. Tested contacts and identified HIV-positives were mostly aged ≥15 years (>99.7%) and females (80.6% of tests, 79.4% of HIV-positives). Most SNS contacts were tested (78,363; 64.7%) and diagnosed (6376; 82.5%) in communities. SNS tests and HIV-positives grew 11.5 and 6.1-fold respectively, from October-December 2021 to January-March 2023, with majority of clients reached in communities vs. facilities (78,763 vs. 42,976). These results indicate that SNS testing is a promising HIV case-finding approach in Tanzania.

INTRODUCTION: A lateral flow rapid diagnostic test (RDT) enables detection of measles specific immunoglobulin M (IgM) antibody in serum, capillary blood, and oral fluid with accuracy consistent with enzyme immunoassay (EIA). The objectives of the study were: 1) to assess measles RDT inter-reader agreement between two clinic staff; 2) to assess the sensitivity and specificity of the measles RDT relative to standard surveillance testing in a low transmission setting; 3) to evaluate the knowledge, attitudes, and practices of staff in clinics using the RDT; and 4) to assess the impact of RDT testing on the measles public health response in Malaysia. MATERIALS AND METHODS: The clinic-based prospective evaluation included all suspected measles cases captured by routine measles surveillance at 34 purposely selected clinics in 15 health districts in Malaysia between September 2019 and June 2020, following day-long regional trainings on RDT use. Following informed consent, four specimens were collected from each suspected case, including those routinely collected for standard surveillance [serum for EIA and throat swabs for quantitative reverse transcriptase polymerase chain reaction (RT-qPCR)] together with capillary blood and oral fluid tested with RDTs during the study. RDT impact was evaluated by comparing the rapidity of measles public health response between the pre-RDT implementation (December 2018 to August 2019) and RDT implementation periods (September 2019 to June 2020). To assess knowledge, attitudes, and practices of RDT use, staff involved in the public health management of measles at the selected sites were surveyed. RESULTS: Among the 436 suspect cases, agreement of direct visual readings of measles RDT devices between two health clinic staff was 99% for capillary blood (k = 0.94) and 97% for oral fluid (k = 0.90) specimens. Of the total, 45 (10%) were positive by measles IgM EIA (n = 44, including five also positive by RT-qPCR) or RT-qPCR only (n = 1), and 38 were positive by RDT (using either capillary blood or oral fluid). Using measles IgM EIA or RT-qPCR as reference, RDT sensitivity using capillary blood was 43% (95% CI: 30%-58%) and specificity was 98% (95% CI: 96%-99%); using oral fluid, sensitivity (26%, 95% CI: 15%-40%) and specificity (97%, 95% CI: 94%-98%) were lower. Nine months after training, RDT knowledge was high among staff involved with the public health management of measles (average quiz score of 80%) and was highest among those who received formal training (88%), followed by those trained during supervisory visits (83%). During the RDT implementation period, the number of days from case confirmation until initiation of public response decreased by about 5 days. CONCLUSION: The measles IgM RDT shows >95% inter-reader agreement, high retention of RDT knowledge, and a more rapid public health response. However, despite ≥95% RDT specificity using capillary blood or oral fluid, RDT sensitivity was <45%. Higher-powered studies using highly specific IgM assays and systematic RT-qPCR for case confirmation are needed to establish the role of RDT in measles elimination settings.

INTRODUCTION: Nutrition program modifications occurred globally in response to the COVID-19 pandemic. Within community management of acute malnutrition (CMAM), community screenings for acute malnutrition were replaced by caregivers monitoring child mid-upper arm circumference (MUAC), but questions remain about different MUAC tapes' performance and acceptability for caregiver use. METHODS: The study was conducted in Central Equatoria and Warrap States, South Sudan, between March 2022 and January 2023. A three-group prospective non-randomized design was used to compare the performance of three MUAC tapes (UNICEF 2009, UNICEF 2020, and GOAL MAMI) used by caregivers. The primary outcome was the false negative rate (i.e., the proportion of children not identified as wasted by the caregiver but classified as wasted by enumerators). Caregivers with children aged 5-53 months were assigned to and trained on the use of 1 of the 3 tapes and followed for 8 months, including three monitoring visits and baseline/endline surveys. RESULTS: Of the 2,893 enrolled children, 2,401 (83.0%) completed baseline, endline, and two or more monitoring visits. Only 3.7% of children were identified as wasted by caregivers and 3.8% by study team measurement. Cumulative measurement agreement between caregivers and enumerators was similar by tape. False negative and false positive rates were both <0.5% overall and similar among the tapes. There were differences in training needs and durability between the tapes, but all three were acceptable and performed equally well. DISCUSSION: Caregiver measurement of child MUAC is feasible in South Sudan. The three MUAC tapes were acceptable, and caregivers could measure accurately with minimal support. All tapes performed similarly and are appropriate for use in Family MUAC programs in South Sudan. There were indications that the UNICEF 2020 tape may be less durable; the GOAL MAMI tape has the added benefit of being suitable for assessments of infants <6 months of age.

Background: Following reports of an outbreak of HIV infection among children in Larkana District, Pakistan, an international team investigated the extent and cause of the outbreak between April and June 2019. Aims: To investigate the incidence of HIV among children in Larkana District, Pakistan and describe the distribution of cases by time, place and person.

BACKGROUND: As part of COVID-19 mitigation strategies, emergency nutrition program adaptations were implemented, but evidence of the effects is limited. Compared to the standard protocol, the full adapted protocol included adapted admissions criteria, simplified dosing, and reduced visit frequency; partially adapted protocols consisting of only some of these modifications were also implemented. To enable evidence-based nutrition program modifications as the context evolved, this study was conducted to characterize how protocol adaptations in South Sudan affected Outpatient Therapeutic Feeding Program outcomes. METHODS: A mixed methods approach consisting of secondary analysis of individual-level nutrition program data and key informant interviews was used. Analyses focused on program implementation and severe acute malnutrition treatment outcomes under the standard, full COVID-19 adapted, and partially adapted treatment protocols from 2019 through 2021. Analyses compared characteristics and outcomes by different admission types under the standard protocol and across four different treatment protocols. Regression models evaluated the odds of recovery and mean length of stay (LoS) under the four protocols. RESULTS: Very few (1.6%; n = 156) children admitted based on low weight-for-height alone under the standard protocol would not have been eligible for admission under the adapted protocol. Compared to the full standard protocol, the partially adapted (admission only) and partially adapted (admission and dosing) protocols had lower LoS of 28.4 days (CI - 30.2, - 26.5) and 5.1 days (CI - 6.2, - 4.0); the full adapted protocol had a decrease of 3.0 (CI - 5.1, - 1.0) days. All adapted protocols had significantly increased adjusted odds ratios (AOR) for recovery compared to the full standard protocol: partially adapted (admission only) AOR = 2.56 (CI 2.18-3.01); partially adapted (admission + dosing) AOR = 1.78 (CI 1.45-2.19); and fully adapted protocol AOR = 2.41 (CI 1.69-3.45). CONCLUSIONS: This study provides evidence that few children were excluded when weight-for-height criteria were suspended. LoS was shortest when only MUAC was used for entry/exit but dosing and visit frequency were unchanged. Significantly shorter LoS with simplified dosing and visit frequency vs. under the standard protocol indicate that protocol adaptations may lead to shorter recovery and program enrollment times. Findings also suggest that good recovery is achievable with reduced visit frequency and simplified dosing.

OBJECTIVE: We assessed the impact of the COVID-19 pandemic and the protocol adaptations on cost and cost-effectiveness of community management of acute malnutrition (CMAM) program in South Sudan. DESIGN: Retrospective program expenditure-based analysis of non-governmental organisation (NGO) CMAM programs for COVID-19 period (April 2020-December 2021) in respect to pre-COVID period (January 2019-March 2020). SETTING: Study was conducted as part of a bigger evaluation study in South Sudan. PARTICIPANTS: International and national NGOs operating CMAM programs under the nutrition cluster participated in the study. RESULTS: The average cost per child recovered from the programme declined by 20 % during COVID from $133 (range: $34-1174) pre-COVID to $107 (range: $20-333) during COVID. The cost per child recovered was negatively correlated with programme size (pre-COVID r-squared = 0·58; during COIVD r-squared = 0·50). Programmes with higher enrollment were cheaper compared with those with low enrolment. Salaries, ready to use food and community activities accounted for over two-thirds of the cost per recovery during both pre-COVID (69 %) and COVID (79 %) periods. While cost per child recovered decreased during COVID period, it did not negatively impact on the programme outcome. Enrolment increased by an average of 19·8 % and recovery rate by 4·6 % during COVID period. CONCLUSIONS: Costs reduced with no apparent negative implication on recovery rates after implementing the COVID CMAM protocol adaptations with a strong negative correlation between cost and programme size. This suggests that investing in capacity, screening and referral at existing CMAM sites to enable expansion of caseload maybe a preferable strategy to increasing the number of CMAM sites in South Sudan.

Pertussis remains a public health concern in South Africa, with an increase in reported cases and outbreaks in recent years. Whole genome sequencing was performed on 32 Bordetella pertussis isolates sourced from three different surveillance programmes in South Africa between 2015 and 2019. Genome sequences were characterized using multilocus sequence typing, vaccine antigen genes (ptxP, ptxA, ptxB, prn and fimH) and overall genome structure. All isolates were sequence type 2 and harboured the pertussis toxin promoter allele ptxP3. The dominant genotype was ptxP3-ptxA1-ptxB2-prn2-fimH2 (31/32, 96.9 %), with no pertactin-deficient or other mutations in vaccine antigen genes identified. Amongst 21 isolates yielding closed genome assemblies, eight distinct genome structures were detected, with 61.9 % (13/21) of the isolates exhibiting three predominant structures. Increases in case numbers are probably not due to evolutionary changes in the genome but possibly due to other factors such as the cyclical nature of B. pertussis disease, waning immunity due to the use of acellular vaccines and/or population immunity gaps.

A non-randomized prospective cohort study was conducted in 2022 to compare recovery rate and length of stay (LoS) for acutely malnourished children treated under South Sudan's standard Community Management of Acute Malnutrition (CMAM) protocol and a COVID-modified protocol. Children aged 6-59 months received acute malnutrition (AM) treatment under the standard or modified protocol (mid-upper-arm circumference-only entry/exit criteria and simplified dosing). Primary (recovery rate and LoS) were compared for outpatient therapeutic (OTP) and therapeutic supplementary feeding programs (TSFP) using descriptive statistics and mixed-effects models. Children admitted to OTP under both protocols were similar in age and sex; children admitted to TSFP were significantly older under the modified protocol than the standard protocol. Shorter LoS and higher recovery rates were observed under the modified protocol for both OTP (recovery: 93.3% vs. 87.2%; LoS: 38.3 vs. 42.8 days) and TSFP (recovery: 79.8% vs. 72.7%; LoS: 54.0 vs. 61.9 days). After adjusting for site and child characteristics, neither differences in adjusted odds of recovery [OTP: 2.63; TSFP 1.80] nor LoS [OTP -10.0; TSFP -7.8] remained significant. Modified protocols for AM performed well. Adjusted models indicate similar treatment outcomes to the standard protocol. Adopting simplified protocols could be beneficial post-pandemic; however, recovery and relapse will need to be monitored.

The U.S. Centers for Disease Control and Prevention in collaboration with the National Malaria Elimination Program and the African Field Epidemiology Network established the Malaria Frontline Project to provide innovative approaches to improve the malaria program implementation in Kano and Zamfara States, Nigeria. Innovative approaches such as malaria bulletin, malaria monitoring wall chart, conduct of ward level data validation meetings and malaria dashboard have helped improve the use of data for decision making at all levels. Innovative approaches deployed during the project implementation facilitated data analysis and a better understanding of malaria program performance and data utilization for decision making at all levels. These innovative approaches may improve malaria control program performance in Nigeria and other resource limited countries. © Adefisoye Adewole et al. Pan African Medical Journal (ISSN: 1937-8688).

INTRODUCTION: The World Health Organization recommended the initiation of antiretroviral therapy (ART) for people living with HIV (PLHIV) regardless of CD4 cell counts. Tanzania adopted this recommendation known as test-and-treat policy in 2016. However, programmatic implementation of this policy has not been assessed since its initiation. The objective of the study was to assess the impact of this policy in Tanzania. METHODS: This was a cross-sectional study among PLHIV aged 15 years and older using routinely collected program data. The dependent variable was interruption in treatment (IIT), defined as no clinical contact for at least 90 days after the last clinical appointment. The main independent variable was test-and-treat policy status which categorized PLHIV into the before and after groups. Co-variates were age, sex, facility type, clinical stage, CD4 count, ART duration, and body mass index. The associations were assessed using the generalized estimating equation with inverse probability weighting. RESULTS: The study involved 33,979 PLHIV-14,442 (42.5%) and 19,537 (57.5%) were in the before and after the policy groups, respectively. Among those who experienced IIT, 4,219 (29%) and 7,322 (38%) were in the before and after the policy groups respectively. Multivariable analysis showed PLHIV after the policy was instated had twice [AOR 2.03; 95%CI 1.74-2.38] the odds of experiencing IIT than those before the policy was adopted. Additionally, higher odds of experiencing IIT were observed among younger adults, males, and those with advanced HIV disease. CONCLUSION: Demographic and clinical status variables were associated with IIT, as well as the test-and-treat policy. To achieve epidemic control, programmatic adjustments on continuity of treatment may are needed to complement the programmatic implementation of the policy.

The transmission patterns of drug-resistant tuberculosis (TB) remain poorly understood, despite over half a million incident cases in 2017. Modeling TB transmission networks can provide insight into the nature and drivers of transmission, but incomplete and non-random sampling of TB cases can pose challenges to making inferences from epidemiologic and molecular data. We conducted a quantitative bias analysis to assess the effect of missing cases on a transmission network inferred from Mtb sequencing data on extensively drug-resistant (XDR) TB cases in South Africa. We tested scenarios in which cases were missing at random, differentially by clinical characteristics, or differentially by transmission (i.e., cases with many links were under or over-sampled). Under the assumption cases were missing at random, cases in the complete, modeled network would have had a mean of 20 or more transmission links, which is far higher than expected, in order to reproduce the observed, partial network. Instead, we found that the most likely scenario involved undersampling of high-transmitting cases, and further models provided evidence for superspreading behavior. This is, to our knowledge, the first study to define and assess the support for different mechanisms of missingness in a study of TB transmission. Our findings should caution interpretation of results of future studies of TB transmission in high-incidence settings, given the potential for biased sampling, and should motivate further research aimed at identifying the specific host, pathogen, or environmental factors contributing to superspreading.

BACKGROUND: The World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear. METHODS: We obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansusceptible) if they were predicted to be susceptible to isoniazid and to the other drugs or if they contained mutations of unknown association in genes that affect susceptibility to the other drugs. We simulated the way in which the negative predictive value changed with the prevalence of drug resistance. RESULTS: A total of 10,209 isolates were analyzed. The largest proportion of phenotypes was predicted for rifampin (9660 [95.4%] of 10,130) and the smallest was predicted for ethambutol (8794 [89.8%] of 9794). Resistance to isoniazid, rifampin, ethambutol, and pyrazinamide was correctly predicted with 97.1%, 97.5%, 94.6%, and 91.3% sensitivity, respectively, and susceptibility to these drugs was correctly predicted with 99.0%, 98.8%, 93.6%, and 96.8% specificity. Of the 7516 isolates with complete phenotypic drug-susceptibility profiles, 5865 (78.0%) had complete genotypic predictions, among which 5250 profiles (89.5%) were correctly predicted. Among the 4037 phenotypic profiles that were predicted to be pansusceptible, 3952 (97.9%) were correctly predicted. CONCLUSIONS: Genotypic predictions of the susceptibility of M. tuberculosis to first-line drugs were found to be correlated with phenotypic susceptibility to these drugs. (Funded by the Bill and Melinda Gates Foundation and others.).

BACKGROUND: Globally, emergency nutrition program adaptations were implemented as part of COVID-19 mitigation strategies, but the implications of the adoption of all protocol changes at scale in the context of deteriorating food security are not yet well characterized. With ongoing conflict, widespread floods, and declining food security, the secondary impacts of COVID-19 on child survival in South Sudan is of great concern. In light of this, the present study aimed to characterize the impact of COVID-19 on nutrition programming in South Sudan. METHODS: A mixed methods approach including a desk review and secondary analysis of facility-level program data was used to analyze trends in program indicators over time and compare two 15-month periods prior to the onset of COVID-19 (January 2019 - March 2020; "pre-COVID period") and after the start of the pandemic (April 2020 - June 2021; "COVID" period) in South Sudan. RESULTS: The median number of reporting Community Management of Acute Malnutrition sites increased from 1167 pre-COVID to 1189 during COVID. Admission trends followed historic seasonal patterns in South Sudan; however, compared to pre-COVID, declines were seen during COVID in total admissions (- 8.2%) and median monthly admissions (- 21.8%) for severe acute malnutrition. For moderate acute malnutrition, total admissions increased slightly during COVID (1.1%) while median monthly admissions declined (- 6.7%). Median monthly recovery rates improved for severe (92.0% pre-COVID to 95.7% during COVID) and moderate acute malnutrition (91.5 to 94.3%) with improvements also seen in all states. At the national level, rates also decreased for default (- 2.4% for severe, - 1.7% for moderate acute malnutrition) and non-recovery (- 0.9% for severe, - 1.1% for moderate acute malnutrition), with mortality rates remaining constant at 0.05-0.15%. CONCLUSIONS: Within the context of the ongoing COVID-19 pandemic in South Sudan, improved recovery, default, and non-responder rates were observed following adoption of changes to nutrition protocols. Policymakers in South Sudan and other resource-constrained settings should consider if simplified nutrition treatment protocols adopted during COVID-19 improved performance and should be maintained in lieu of reverting to standard treatment protocols.

HIV prevalence among the general population in South Sudan, the world's newest country, is estimated at 2.9% and in Nimule, a town at the border with Uganda, it is estimated at 7.5%. However, there is limited data describing the HIV epidemic among female sex workers and sexually exploited adolescents (FSW/SEA) in the country. This study was conducted using a respondent-driven sampling (RDS) among FSW/SEA aged ≥15 years in January-February 2017 who sold or exchanged sex in the last six months in Nimule. Consenting participants were administered a questionnaire and tested for HIV according to the national algorithm. Syphilis testing was conducted using SD BIOLINE Syphilis 3.0 and Rapid Plasma Reagin for confirmation. Data were analyzed in SAS and RDS-Analyst and weighted results are presented. The 409 FSW/SEA participants with a median age of 28 years (IQR 23-35) and a median age of 23 years (IQR 18-28) when they entered the world of sex work, were enrolled in the Eagle survey. Nearly all (99.2%) FSW/SEA lacked comprehensive knowledge of HIV though almost half (48.5%) talked to a peer educator or outreach worker about HIV in the last 30 days. More than half (55.3%) were previously tested for HIV. Only 46.4% used a condom during their last vaginal or anal sexual act with a client. One in five (19.8%) FSW/SEA experienced a condom breaking during vaginal or anal sex in the last six months HIV prevalence was 24.0% (95% CI: 19.4-28.5) and 9.2% (95% CI: 6.5-11.9) had active syphilis. The multivariable analysis revealed the association between HIV and active syphilis (aOR: 6.99, 95% CI: 2.23-21.89). HIV and syphilis prevalence were higher among FSW/SEA in Nimule than the general population in the country and Nimule. Specifically, the HIV prevalence was eight times higher than the general population. Our findings underscore the importance of providing HIV and syphilis testing for FSW/SEA in conjunction with comprehensive combination prevention, including comprehensive HIV information, promotion of condom use, and availing treatment services for both HIV and syphilis.

Following the certification of the World Health Organization Region of Africa as free of serotype 1 wild poliovirus (WPV1) in 2020, Afghanistan and Pakistan represent the last remaining WPV1 reservoirs. As efforts continue in these countries to progress to eradication, there is an opportunity for a deeper understanding of the spatiotemporal characteristics and epidemiological risk factors associated with continual WPV1 circulation in the region. Using poliovirus surveillance data from 2017-2019, we used pairwise comparisons of VP1 nucleotide sequences to illustrate the spatiotemporal WPV1 dispersal to identify key sources and destinations of potentially infected, highly mobile populations. We then predicted the odds of WPV1 detection at the district level using a generalized linear model with structural indicators of health, security, environment, and population demographics. We identified evidence of widespread population mobility based on WPV1 dispersal within and between the countries, and evidence indicating five districts in Afghanistan (Arghandab, Batikot, Bermel, Muhamandara and Nawzad) and four districts in Pakistan (Charsada, Dera Ismail Khan, Killa Abdullah and Khyber) act as cross-border WPV1 circulation reservoirs. We found that the probability of detecting WPV1 in a district increases with each armed conflict event (OR = 1.024, +- 0.008), level of food insecurity (OR = 1.531, +-0.179), and mean degrees Celsius during the months of greatest precipitation (OR = 1.079, +- 0.019). Our results highlight the multidisciplinary complexities contributing to the continued transmission of WPV1 in Afghanistan and Pakistan. We discuss the implications of our results, stressing the value of coordination during this final chapter of the wild polio virus eradication initiative.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (73%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (07%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (914%), moxifloxacin (916%) and ethambutol (933%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation. 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

PURPOSE OF REVIEW: We describe the impact of COVID-19 on PEPFAR programs in Africa and how PEPFAR adapted and leveraged its interventions to the changing landscape of the COVID-19 pandemic. RECENT FINDINGS: To mitigate the potential impact of COVID-19 on the HIV response and protect the gains, continuity of treatment was the guiding principle regarding the provision of services in PEPFAR-supported countries. As the COVID-19 pandemic matured, PEPFAR's approach evolved from a strictly "protect and salvage" approach to a "restore and accelerate" approach that embraced innovative adaptations in service and "person-centered" care. The impact of service delivery interruptions caused by COVID-19 on progress towards HIV epidemic control in PEPFAR-supported African countries remains undetermined. With COVID vaccine coverage many months away and more transmissible variants being reported, Africa may experience more pandemic surges. HIV programs will depend on nimble and innovative adaptations in prevention and treatment services in order to advance epidemic control objectives.

Bedaquiline Drug Resistance Emergence Assessment in Multidrug-resistant-tuberculosis (MDR-TB) (DREAM) was a 5-year (2015-2019) phenotypic drug-resistance surveillance study across 11 countries. DREAM assessed the susceptibility of 5036 MDR-TB isolates of bedaquiline-treatment-naïve patients to bedaquiline and other anti-tuberculosis drugs by the 7H9 broth microdilution (BMD) and 7H10/7H11 agar dilution (AD) minimal inhibitory concentration (MIC) methods. Bedaquiline AD MIC quality control (QC) range for the H37Rv reference strain was unchanged, but the BMD MIC QC range (0.015-0.12 μg/ml) was adjusted compared with ranges from a multilaboratory, multicountry reproducibility study conforming to Clinical and Laboratory Standards Institute Tier-2 criteria. Epidemiological cut-off values of 0.12 μg/ml by BMD and 0.25 μg/ml by AD were consistent with previous bedaquiline breakpoints. An area of technical uncertainty or Intermediate category was set at 0.25 μg/ml and 0.5 μg/ml for BMD and AD, respectively. When applied to the 5036 MDR-TB isolates, bedaquiline-susceptible, intermediate and bedaquiline-resistant rates were 97.9%, 1.5% and 0.6%, respectively, for BMD, and 98.8%, 0.8% and 0.4% for AD. Resistance rates were: ofloxacin 35.1%, levofloxacin 34.2%, moxifloxacin 33.3%, 1.5% linezolid and 2% clofazimine. Phenotypic cross resistance between bedaquiline and clofazimine was 0.4% in MDR-TB and 1% in pre-extensively drug-resistant (pre-XDR-TB)/XDR-TB populations. Co-resistance to bedaquiline and linezolid, and clofazimine and linezolid, were 0.1% and 0.3%, respectively, in MDR-TB, and 0.2% and 0.4% in pre-XDR-TB/XDR-TB populations. Resistance rates to bedaquiline appear to be low in the bedaquiline-treatment-naïve population. No treatment-limiting patterns for cross-resistance and co-resistance have been identified with key TB drugs to date.

Pyrethroid resistance is widespread in malaria vectors. However, differential mortality in discriminating dose assays to different pyrethroids is often observed in wild populations. When this occurs, it is unclear if this differential mortality should be interpreted as an indication of differential levels of susceptibility within the pyrethroid class, and if so, if countries should consider selecting one specific pyrethroid for programmatic use over another. A review of evidence from molecular studies, resistance testing with laboratory colonies and wild populations, and mosquito behavioural assays were conducted to answer these questions. Evidence suggested that in areas where pyrethroid resistance exists, different results in insecticide susceptibility assays with specific pyrethroids currently in common use (deltamethrin, permethrin, α-cypermethrin, and λ-cyhalothrin) are not necessarily indicative of an operationally relevant difference in potential performance. Consequently, it is not advisable to use rotation between these pyrethroids as an insecticide-resistance management strategy. Less commonly used pyrethroids (bifenthrin and etofenprox) may have sufficiently different modes of action, though further work is needed to examine how this may apply to insecticide resistance management.

In South Africa, Candida auris was the third most common cause of candidemia in 2016-2017. We performed single nucleotide polymorphism (SNP) genome-wide analysis of 115 C. auris isolates collected between 2009 and 2018 from national laboratory-based surveillance, an environmental survey at four hospitals and a colonization study during a neonatal unit outbreak. The first known South African C. auris strain from 2009 clustered in clade IV. Overall, 98 strains clustered within clade III (85%), 14 within clade I (12%) and three within clade IV (3%). All environmental and colonizing strains clustered in clade III. We also identified known clade-specific resistance mutations in the ERG11 and FKS1 genes. Identification of clade I strains between 2016 and 2018 suggests introductions from South Asia followed by local transmission. SNP analysis characterized most C. auris strains into clade III, the clade first reported from South Africa, but the presence of clades I and IV strains also suggest early introductions from other regions.

BACKGROUND: Studies have shown that drug-resistant tuberculosis (DR-TB) in South Africa (SA) is clonal and is caused mostly by transmission. Identifying transmission chains is important in controlling DR-TB. This study reports on the sentinel molecular surveillance data of Rifampicin-Resistant (RR) TB in SA, aiming to describe the RR-TB strain population and the estimated transmission of RR-TB cases. METHOD: RR-TB isolates collected between 2014 and 2018 from eight provinces were genotyped using combination of spoligotyping and 24-loci mycobacterial interspersed repetitive-units-variable-number tandem repeats (MIRU-VNTR) typing. RESULTS: Of the 3007 isolates genotyped, 301 clusters were identified. Cluster size ranged between 2 and 270 cases. Most of the clusters (247/301; 82.0%) were small in size (< 5 cases), 12.0% (37/301) were medium sized (5-10 cases), 3.3% (10/301) were large (11-25 cases) and 2.3% (7/301) were very large with 26-270 cases. The Beijing genotype was responsible for majority of RR-TB cases in Western and Eastern Cape, while the East-African-Indian-Somalian (EAI1_SOM) genotype accounted for a third of RR-TB cases in Mpumalanga. The overall proportion of RR-TB cases estimated to be due to transmission was 42%, with the highest transmission-rate in Western Cape (64%) and the lowest in Northern Cape (9%). CONCLUSION: Large clusters contribute to the burden of RR-TB in specific geographic areas such as Western Cape, Eastern Cape and Mpumalanga, highlighting the need for community-wide interventions. Most of the clusters identified in the study were small, suggesting close contact transmission events, emphasizing the importance of contact investigations and infection control as the primary interventions in SA.

The novel coronavirus disease 2019, COVID-19, which is caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2) [1] was first reported in December 2019 by Chinese Health Authorities following an outbreak of pneumonia of unknown origin in Wuhan, Hubei Province [2,3]. SARS-CoV-2 is likely of zoonotic origin, similar to SARS and Middle East Respiratory Syndrome (MERS), and transmitted between humans through respiratory droplets and fomites. Since its emergence, it has rapidly spread globally [4].

BACKGROUND: In 2013, the Nigeria Federal Ministry of Health established a Master Health Facility List (MHFL) as recommended by WHO. Since then, some health facilities (HFs) have ceased functioning and new facilities were established. We updated the MHFL and assessed service delivery parameters in the Malaria Frontline Project implementing areas in Kano and Zamfara States. METHODS: We assessed all HFs in each of the 34 project local government areas (LGAs) between July and September 2017. Project staff administered a semi-structured questionnaire developed for this assessment to heads of HFs about the type of facility, category and number of staff working at the facility and to record geo-coordinates of facility. RESULTS: In the Kano State project area, 726 HFs were identified and geo-located: 31 were new facilities, 608 (84%), 116 (16%) and two (0.3%) were Primary Health Care (PHC), secondary and tertiary facilities respectively. Using the national definition, there were 710 (98%) functional facilities and 644 (91%) of these reported to the national health information platform, District Health Information System, version 2 (DHIS2). The Zamfara project area had 739 HFs: eight were new, 715 (97%), 22 (3.0%) and two (0.2%) PHCs, secondary and tertiary facilities respectively. There were 695 (94%) functional facilities with 656 (94%) of these reporting to DHIS2. Using national criteria for primary health care designation, only 95 (9%) of all PHCs in the two States met the minimum human resource requirements. CONCLUSION: Most HFs were functional and reported to DHIS2. A comprehensive MHFL having all the important parameters that should be established and updated regularly by authorities to make it more useful for health services administration and management. Most functional facilities are understaffed.

Transmission patterns of drug-resistant tuberculosis (TB) remain poorly understood, despite over half a million incident cases in 2017. Modeling TB transmission networks can provide insight into drivers of transmission, but incomplete sampling of TB cases can pose challenges for inference from individual epidemiologic and molecular data. We assessed the effect of missing cases on a transmission network inferred from Mycobacterium tuberculosis sequencing data on extensively drug-resistant TB cases in KwaZulu-Natal, South Africa diagnosed in 2011-2014. We tested scenarios in which cases were missing at random, differentially by clinical characteristics or by transmission (i.e., cases with many links were under or over-sampled). Under the assumption cases were missing randomly, the mean number of transmissions per case in the complete network needed to be larger than 20, far higher than expected, to reproduce the observed network. Instead, the most likely scenario involved undersampling of high-transmitting cases and models provided evidence for superspreading. This is the first study to assess support for different mechanisms of missingness in a TB transmission study, but our results are subject to the distributional assumptions of the network models we used. Transmission studies should consider the potential biases introduced by incomplete sampling and identify host, pathogen, or environmental factors driving superspreading.

BACKGROUND: An outbreak of listeriosis was identified in South Africa in 2017. The source was unknown. METHODS: We conducted epidemiologic, trace-back, and environmental investigations and used whole-genome sequencing to type Listeria monocytogenes isolates. A case was defined as laboratory-confirmed L. monocytogenes infection during the period from June 11, 2017, to April 7, 2018. RESULTS: A total of 937 cases were identified, of which 465 (50%) were associated with pregnancy; 406 of the pregnancy-associated cases (87%) occurred in neonates. Of the 937 cases, 229 (24%) occurred in patients 15 to 49 years of age (excluding those who were pregnant). Among the patients in whom human immunodeficiency virus (HIV) status was known, 38% of those with pregnancy-associated cases (77 of 204) and 46% of the remaining patients (97 of 211) were infected with HIV. Among 728 patients with a known outcome, 193 (27%) died. Clinical isolates from 609 patients were sequenced, and 567 (93%) were identified as sequence type 6 (ST6). In a case-control analysis, patients with ST6 infections were more likely to have eaten polony (a ready-to-eat processed meat) than those with non-ST6 infections (odds ratio, 8.55; 95% confidence interval, 1.66 to 43.35). Polony and environmental samples also yielded ST6 isolates, which, together with the isolates from the patients, belonged to the same core-genome multilocus sequence typing cluster with no more than 4 allelic differences; these findings showed that polony produced at a single facility was the outbreak source. A recall of ready-to-eat processed meat products from this facility was associated with a rapid decline in the incidence of L. monocytogenes ST6 infections. CONCLUSIONS: This investigation showed that in a middle-income country with a high prevalence of HIV infection, L. monocytogenes caused disproportionate illness among pregnant girls and women and HIV-infected persons. Whole-genome sequencing facilitated the detection of the outbreak and guided the trace-back investigations that led to the identification of the source.

Objective: To describe the epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) healthcare-associated infections (HAI) in Egyptian hospitals reporting to the national HAI surveillance system. Methods: Design: Descriptive analysis of CRE HAIs and retrospective observational cohort study using national HAI surveillance data. Setting: Egyptian hospitals participating in the HAI surveillance system. The patient population included patients admitted to the intensive care unit (ICU) in participating hospitals. Enterobacteriaceae HAI cases were Klebsiella, Escherichia coli, and Enterobacter isolates from blood, urine, wound or respiratory specimen collected on or after day 3 of ICU admission. CRE HAI cases were those resistant to at least one carbapenem. For CRE HAI cases reported during 2011-2017, a hospital-level and patient-level analysis were conducted using only the first CRE isolate by pathogen and specimen type for each patient. For facility, microbiology, and clinical characteristics, frequencies and means were calculated among CRE HAI cases and compared with carbapenem-susceptible Enterobacteriaceae HAI cases through univariate and multivariate logistic regression using STATA 13. Results: There were 1598 Enterobacteriaceae HAI cases, of which 871 (54.1%) were carbapenem resistant. The multivariate regression analysis demonstrated that carbapenem resistance was associated with specimen type, pathogen, location prior to admission, and length of ICU stay. Between 2011 and 2017, there was an increase in the proportion of Enterobacteriaceae HAI cases due to CRE (p-value = 0.003) and the incidence of CRE HAIs (p-value = 0.09). Conclusions: This analysis demonstrated a high and increasing burden of CRE in Egyptian hospitals, highlighting the importance of enhancing infection prevention and control (IPC) programs and antimicrobial stewardship activities and guiding the implementation of targeted IPC measures to contain CRE in Egyptian ICU's .

Antimicrobial-resistant (AMR) infections pose a major threat to global public health. Similar to other AMR pathogens, both historical and ongoing drug-resistant tuberculosis (TB) epidemics are characterized by transmission of a limited number of predominant Mycobacterium tuberculosis (Mtb) strains. Understanding how these predominant strains achieve sustained transmission, particularly during the critical period before they are detected via clinical or public health surveillance, can inform strategies for prevention and containment. In this study, we employ whole-genome sequence (WGS) data from TB clinical isolates collected in KwaZulu-Natal, South Africa to examine the pre-detection history of a successful strain of extensively drug-resistant (XDR) TB known as LAM4/KZN, first identified in a widely reported cluster of cases in 2005. We identify marked expansion of this strain concurrent with the onset of the generalized HIV epidemic 12 y prior to 2005, localize its geographic origin to a location in northeastern KwaZulu-Natal approximately 400 km away from the site of the 2005 outbreak, and use protein structural modeling to propose a mechanism for how strain-specific rpoB mutations offset fitness costs associated with rifampin resistance in LAM4/KZN. Our findings highlight the importance of HIV coinfection, high preexisting rates of drug-resistant TB, human migration, and pathoadaptive evolution in the emergence and dispersal of this critical public health threat. We propose that integrating whole-genome sequencing into routine public health surveillance can enable the early detection and local containment of AMR pathogens before they achieve widespread dispersal.

This manuscript describes the Child Health and Mortality Prevention Surveillance (CHAMPS) network approach to pathologic evaluation of minimally invasive tissue sampling (MITS) specimens, including guidelines for histopathologic examination and further diagnostics with special stains, immunohistochemistry, and molecular testing, as performed at the CHAMPS Central Pathology Laboratory (CPL) at the Centers for Disease Control and Prevention, as well as techniques for virtual discussion of these cases (telepathology) with CHAMPS surveillance locations. Based on review of MITS from the early phase of CHAMPS, the CPL has developed standardized histopathology-based algorithms for achieving diagnoses from MITS and telepathology procedures in conjunction with the CHAMPS sites, with the use of whole slide scanners and digital image archives, for maximizing concurrence and knowledge sharing between site and CPL pathologists. These algorithms and procedures, along with lessons learned from initial implementation of these approaches, guide pathologists at the CPL and CHAMPS sites through standardized diagnostics of MITS cases, and allow for productive, real-time case discussions and consultations.