Seasonal malaria chemoprevention in a context of high presumed sulfadoxine-pyrimethamine resistance: malaria morbidity and molecular drug resistance profiles in South Sudan.

BACKGROUND: Seasonal malaria chemoprevention (SMC) using sulfadoxine-pyrimethamine plus amodiaquine (SP-AQ), is a community-based malaria preventive strategy commonly used in the Sahel region of sub-Saharan Africa. However, to date it has not been implemented in East Africa due to high SP resistance levels. This paper is a report on the implementation of SMC outside of the Sahel in an environment with a high level of presumed SP-resistance: five cycles of SMC using SPAQ were administered to children 3-59 months during a period of high malaria transmission (July-December 2019) in 21 villages in South Sudan. METHODS: A population-based SMC coverage survey was combined with a longitudinal time series analysis of health facility and community health data measured after each SMC cycle. SMC campaign effectiveness was assessed by Poisson model. SPAQ molecular resistance markers were additionally analysed from dried blood spots from malaria confirmed patients. RESULTS: Incidence of uncomplicated malaria was reduced from 6.6 per 100 to an average of 3.2 per 100 after SMC administration (mean reduction: 53%) and incidence of severe malaria showed a reduction from 21 per 10,000 before SMC campaign to a mean of 3.3 per 10,000 after each cycle (mean reduction: 84%) in the target group when compared to before the SMC campaign. The most prevalent molecular haplotype associated with SP resistance was the IRNGE haplotype (quintuple mutant, with 51I/59R/108N mutation in pfdhfr + 437G/540E in pfdhps). In contrast, there was a low frequency of AQ resistance markers and haplotypes resistant to both drugs combined (< 2%). CONCLUSIONS: The SMC campaign was effective and could be used as an additional preventive tool in seasonal malaria settings outside of the Sahel, especially in areas where access to health care is unstable. Malaria case load reduction was observed despite the high level of resistance to SP.

Screening for K13-Propeller Mutations Associated with Artemisinin Resistance in Plasmodium falciparum in Yambio County (Western Equatoria State, South Sudan).

Artemisinin-combined treatments are the recommended first-line treatment of Plasmodium falciparum malaria, but they are being threatened by emerging artemisinin resistance. Mutations in pfk13 are the principal molecular marker for artemisinin resistance. This study characterizes the presence of mutations in pfk13 in P. falciparum in Western Equatoria State, South Sudan. We analyzed 468 samples from patients with symptomatic malaria and found 15 mutations (8 nonsynonymous and 7 synonymous). Each mutation appeared only once, and none were validated or candidate markers of artemisinin resistance. However, some mutations were in the same or following position of validated and candidate resistance markers, suggesting instability of the gene that could lead to resistance. The R561L nonsynonymous mutation was found in the same position as the R561H validated mutation. Moreover, the A578S mutation, which is widespread in Africa, was also reported in this study. We found a high diversity of other pfk13 mutations in low frequency. Therefore, routine molecular surveillance of resistance markers is highly recommended to promptly detect the emergence of resistance-related mutations and to limit their spread.

Plasmodium falciparum pfhrp2 and pfhrp3 Gene Deletions in Malaria-Hyperendemic Region, South Sudan.

Pfhrp2 and pfhrp3 gene deletions threaten the use of Plasmodium falciparum malaria rapid diagnostic tests globally. In South Sudan, deletion frequencies were 15.6% for pfhrp2, 20.0% for pfhrp3, and 7.5% for double deletions. Deletions were approximately twice as prevalent in monoclonal infections than in polyclonal infections.

Viral suppression and HIV-1 drug resistance 1 year after pragmatic transitioning to dolutegravir first-line therapy in Malawi: a prospective cohort study.

BACKGROUND: Many countries are now replacing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line antiretroviral therapy (ART) with a regimen containing tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD). Recognising laboratory limitations, Malawi opted to transition those on NNRTI-based first-line ART to TLD without viral load testing. We aimed to assess viral load and HIV drug resistance during 1 year following transition to TLD without previous viral load testing. METHODS: In this prospective cohort study, we monitored 1892 adults transitioning from NNRTI-based first-line ART to the TLD regimen in the Médecins Sans Frontières-supported decentralised HIV programme in Chiradzulu District, Malawi. Eligible adults were enrolled between Jan 17 and May 11, 2019, at Ndunde and Milepa health centres, and between March 8 and May 11, 2019, at the Boma clinic. Viral load at the start of the TLD regimen was assessed retrospectively and measured at month 3, 6, and 12, and additionally at month 18 for those ever viraemic (viral load ≥50 copies per mL). Dolutegravir minimal plasma concentrations (Cmin) were determined for individuals with viraemia. Drug-resistance testing was done at the start of TLD regimen and at viral failure (viral load ≥50 copies per mL, followed by viral load ≥500 copies per mL; resistance defined as Stanford score ≥15). FINDINGS: Of 1892 participants who transitioned to the TLD regimen, 101 (5·3%) were viraemic at TLD start. 89 of 101 had drug-resistance testing with 31 participants (34·8%) with Lys65Arg mutation, 48 (53·9%) with Met184Val/Ile, and 42 (40·4%) with lamivudine and tenofovir disoproxil fumerate dual resistance. At month 12 (in the per-protocol population), 1725 (97·9% [95% CI 97·1-98·5]) of 1762 had viral loads of less than 50 copies per mL, including 83 (88·3% [80·0-94·0]) of 94 of those who were viraemic at baseline. At month 18, 35 (97·2% [85·5-99·9]) of 36 who were viraemic at TLD start with lamivudine and tenofovir disoproxil fumarate resistance and 27 (81·8% [64·5-93·0]) of 33 of those viraemic at baseline without resistance had viral load suppression. 14 of 1838 with at least two viral load tests upon transitioning had viral failure (all with at least one dolutegravir Cmin value <640 ng/mL; active threshold), suggesting suboptimal adherence. High baseline viral load was associated with viral failure (adjusted odds ratio [aOR] 14·1 [2·3-87·4] for 1000 to <10 000 copies per mL; aOR 64·4 [19·3-215·4] for ≥10 000 copies per mL). Two people with viral failure had dolutegravir resistance at 6 months (Arg263Lys or Gly118Arg mutation), both were viraemic with lamivudine and tenofovir disoproxil fumarate resistance at baseline. INTERPRETATION: High viral load suppression 1 year after introduction of the TLD regimen supports the unconditional transition strategy in Malawi. However, high pre-transition viral load, ongoing adherence challenges, and possibly existing nucleoside reverse transcriptase inhibitor resistance can lead to rapid development of dolutegravir resistance in a few individuals. This finding highlights the importance of viral load monitoring and dolutegravir-resistance surveillance after mass transitioning to the TLD regimen. FUNDING: Médecins Sans Frontières. TRANSLATIONS: For the French and Portuguese translations of the abstract see Supplementary Materials section.

Severity, symptomatology, and treatment duration for mental health disorders: a retrospective analysis from a conflict-affected region of northern Nigeria.

BACKGROUND: Mental Health and psychosocial support (MHPSS) programs are essential during humanitarian crises and in conflict settings, like Nigeria's Borno State. However, research on how types of traumatic stress and symptom severity affect clinical improvement is lacking in these contexts, as is consensus over how long these patients must engage in mental health care to see results. METHODS: Records from 11,709 patients from the MHPSS program in Pulka and Gwoza local government areas in Borno State, Nigeria from 2018 and 2019 were retrospectively analyzed. Patient information, symptoms, stress type, severity (CGI-S scale), and clinical improvement (CGI-I and MHGS scales) were assessed by the patient and counselor. Associations between variables were investigated using logistic regression models. RESULTS: Clinical improvement increased with consultation frequency (OR: 2.5, p < 0.001 for CGI-I; OR: 2, p < 0.001 for MHGS), with patients who received three to six counseling sessions were most likely to improve, according to severity. Survivors of sexual violence, torture, and other conflict/violence-related stressors were nearly 20 times as likely to have posttraumatic stress disorder (PTSD) (OR: 19.7, p < 0.001), and depression (OR: 19.3, p < 0.001) symptomatology. Children exposed to conflict-related violence were also almost 40 times as likely to have PTSD (OR: 38.2, p = 0.002). Most patients presented an improvement in outcome at discharge, per both counselors (92%, CGI-I) and self-rating scores (73%, MHGS). CONCLUSION: We demonstrate a threshold at which patients were most likely to improve (3 sessions for mild or moderate patients; 6 sessions for severe). In addition, we identify the specific types of stress and symptom severity that affected the number of sessions needed to achieve successful outcomes, and highlight that some stress types (especially torture or having a relative killed) were specifically linked to PTSD and depression. Therefore, we emphasize the importance of classifying patient stress type and severity to identify the appropriate duration of care needed.

Shifting to Tele-Mental Health in humanitarian and crisis settings: an evaluation of Médecins Sans Frontières experience during the COVID-19 pandemic.

BACKGROUND: 'Tele-Mental Health (MH) services,' are an increasingly important way to expand care to underserved groups in low-resource settings. In order to continue providing psychiatric, psychotherapeutic and counselling care during COVID-19-related movement restrictions, Médecins Sans Frontières (MSF), a humanitarian medical organization, abruptly transitioned part of its MH activities across humanitarian and resource-constrained settings to remote format. METHODS: From June-July of 2020, investigators used a mixed method, sequential explanatory study design to assess MSF staff perceptions of tele-MH services. Preliminary quantitative results influenced qualitative question guide design. Eighty-one quantitative online questionnaires were collected and a subset of 13 qualitative follow-up in-depth interviews occurred. RESULTS: Respondents in 44 countries (6 geographic regions), mostly from Sub-Saharan Africa (39.5%), the Middle East and North Africa (18.5%) and Asia (13.6%) participated. Most tele-MH interventions depended on audio-only platforms (80%). 30% of respondents reported that more than half of their patients were unreachable using these interventions, usually because of poor network coverage (73.8%), a lack of communication devices (72.1%), or a lack of a private space at home (67.2%). Nearly half (47.5%) of respondents felt their staff had a decreased ability to provide comprehensive MH care using telecommunication platforms. Most respondents thought MH staff had a negative (46%) or mixed (42%) impression of remote care. Nevertheless, almost all respondents (96.7%) thought tele-MH services had some degree of usefulness, notably improved access to care (37.7%) and time efficiency (32.8%). Qualitative results outlined a myriad of challenges, notably in establishing therapeutic alliance, providing care for vulnerable populations and those inherent to the communications infrastructure. CONCLUSION: Tele-MH services were perceived to be a feasible alternative solution to in-person therapeutic interventions in humanitarian settings during the COVID-19 pandemic. However, they were not considered suitable for all patients in the contexts studied, especially survivors of sexual or interpersonal violence, pediatric and geriatric cases, and patients with severe MH conditions. Audio-only technologies that lacked non-verbal cues were particularly challenging and made risk assessment and emergency care more difficult. Prior to considering tele-MH services, communications infrastructure should be assessed, and comprehensive, context-specific protocols should be developed.

Erratum: Competency-based mental health supervision: evidence-based tool needs for the humanitarian context - ERRATUM.

[This corrects the article DOI: 10.1017/gmh.2022.23.].

High levels of viral repression, malnutrition and second-line ART use in adolescents living with HIV: a mixed methods study from Myanmar.

BACKGROUND: Adolescents living with HIV/AIDS (ALHIV) are a particularly vulnerable but often overlooked group in the HIV response despite additional disease management challenges. METHODS: All ALHIV (10-19 years), on ART for ≥6 months, presenting to care at a Médecins Sans Frontières (MSF) clinic in Myanmar from January-April 2016 were eligible for the quantitative study component (clinical history, medical examination, laboratory investigation). A subset of these respondents were invited to participate in qualitative interviews. Interviews and focus groups were also conducted with other key informants (care givers, clinicians). RESULTS: Of 177 ALHIV, 56% (100) were aged 9-13 years and 77 (44%) were 14-19. 49% (86) had been orphaned by one parent, and 19% (33) by both. 59% (104) were severely underweight (BMI < 16). 47% presented with advanced HIV (WHO stage III/IV). 93% were virally supressed (< 250 copies/mL). 38 (21%) of ALHIV were on a second-line ART after first-line virological failure. Qualitative interviewing highlighted factors limiting adherence and the central role that HIV counsellors play for both ALHIV patients and caregivers. CONCLUSIONS: Our study shows good clinical, immunological, and virological outcomes for a cohort of Myanmar adolescents living with HIV, despite a majority being severely underweight, presenting with Stage III or IV illness, and the prevalence of comorbid infections (TB). Many treatment and adherence challenges were articulated in qualitative interviewing but emphasized the importance of actively engaging adolescents in their treatment. Comprehensive HIV care for this population must include routine viral load testing and social support programs.

Extremely low hepatitis C prevalence among HIV co-infected individuals in four countries in sub-Saharan Africa.

: A multicentric, retrospective case-series analysis (facility-based) in five sites across Kenya, Malawi, Mozambique, and Uganda screened HIV-positive adults for hepatitis C virus (HCV) antibodies using Oraquick rapid testing and viral confirmation (in three sites). The results reveal a substantially lower prevalence than previously reported for these countries, suggesting that targeted integration of HCV screening in African HIV programs may be more impactful than routine screening.

Increased hepatitis C virus co-infection and injection drug use in HIV-infected fishermen in Myanmar.

BACKGROUND: In Southeast Asia, though fishermen are known to be a key population at high risk of HIV, little is known about their co-infection rates with Hepatitis C virus (HCV), or how illness and risk behaviors vary by occupation or type of fishermen. In Myanmar, this lack of knowledge is particularly acute, despite the fact that much of the country's border is coastline. METHODS: We conducted a retrospective analysis to assess clinical, demographic, and risk characteristics of HIV-infected, ≥15-year-old males under HIV care from 2004 to 2014. Subgroups of fishermen were categorized according to the location of fishing activities, boat ownership, and length of time at sea. Generalized linear models assessed odds of high risk behaviors, including MSM (men who have sex with men), transactional sex, injection drug use (IDU), and HCV co-infection among international, local subsistence, and national migrant fishermen. RESULTS: Of 2798 adult males who enrolled in HIV care between 2004 and 2014, 41.9% (n = 1172) were fishermen. Among these, migrants had the highest odds of engaging in risk behaviors such as sex work (Myanmar national migrants: OR 3.26 95% CI: 2.20 to 4.83), and injecting drugs (international migrants: OR 2.93, 95% CI: 1.22 to 3.87) when compared to the general male HIV clinic population. 15.9% of all fishermen reported past or current IDU (23.0% of international migrants). 22.8% of all fishermen were also co-infected with HCV, and though predictably injectors had the highest odds (OR 20.1, 95% CI: 13.7 to 29.5), even after controlling for other risk factors, fishermen retained higher odds (OR 2.37 95% CI: 1.70 to 3.32). CONCLUSIONS: HIV positive fishermen in Myanmar had higher odds of HCV co-infection. They also disproportionally injected drugs and engaged in transactional sex more than other patients. This is especially pronounced among international migrant fishermen. HIV-infected fishermen should be counseled on high risk activities, screened for HCV, and targeted by harm reduction programs.

High Proportions of Patients With Advanced HIV Are Antiretroviral Therapy Experienced: Hospitalization Outcomes From 2 Sub-Saharan African Sites.

Background: Human immunodeficiency virus (HIV) remains an important cause of hospitalization and death in low- and middle- income countries. Yet morbidity and in-hospital mortality patterns remain poorly characterized, with prior antiretroviral therapy (ART) exposure and treatment failure status largely unknown. Methods: We studied HIV-infected inpatients aged ≥13 years from cohorts in Kenya and the Democratic Republic of Congo (DRC), assessing clinical and demographic characteristics and hospitalization outcomes. Kenyan inpatients were prospectively enrolled during hospitalization; identical retrospective data were extracted for Congolese patients meeting the study criteria using routine medical information. Results: Among 338 HIV-infected patients in Kenya and 411 in DRC, 83.7% (95% confidence interval [CI], 79.4%-87.3%) and 97.3% (95% CI, 95.2%-98.5%), were admitted with advanced disease (defined as CD4 <200 cells/µL or World Health Organization stage 3/4 illness). Among inpatients with advanced HIV, 35.4% and 21.7% were ART-naive at admission. Patients under care had a median time of 44.1 (interquartile range [IQR], 18.4-90.5) months and 55.9 (IQR, 28.1-99.6) months on treatment; 17.2% (95% CI, 13.5%-21.6%) and 29.6% (95% CI, 25.4%-34.3%) died, 25.9% (95% CI, 16.0%-39.0%) and 22.5% (95% CI, 15.8%-31.0%) of these within 48 hours. Conclusions: Across 2 diverse clinical contexts in sub-Saharan Africa, advanced HIV inpatients were frequently admitted with low CD4 counts, often failing first-line ART. Earlier identification of treatment failure and rapid switching to second-line ART are needed.

Long-term clinical, immunological and virological outcomes of patients on antiretroviral therapy in southern Myanmar.

OBJECTIVE: To study the long-term clinical, immunological and virological outcomes among people living with HIV on antiretroviral therapy (ART) in Myanmar. METHODS: A retrospective analysis of people on ART for >9 years followed by a cross-sectional survey among the patients in this group who remained on ART at the time of the survey. Routinely collected medical data established the baseline clinical and demographic characteristics for adult patients initiating ART between 2004 and 2006. Patients remaining on ART between March-August 2015 were invited to participate in a survey assessing clinical, virological, immunological, and biochemical characteristics. RESULTS: Of 615 patients included in the retrospective analysis, 35 (6%) were lost-to-follow-up, 9 (1%) were transferred, 153 died (25%) and 418 (68%) remained active in care. Among deaths, 48 (31.4%) occurred within 3 months of ART initiation, and 81 (52.9%) within 12 months, 90.1% (n = 73) of which were initially classified as stage 3/4. Of 385 patients included in the survey, 30 (7.7%) were on second-line ART regimen; 373 (96.8%) had suppressed viral load (<250 copies/ml). The mean CD4 count was 548 cells/ mm3 (SD 234.1) after ≥9 years on treatment regardless of the CD4 group at initiation. Tuberculosis while on ART was diagnosed in 187 (48.5%); 29 (7.6%) had evidence of hepatitis B and 53 (13.9%) of hepatitis C infection. CONCLUSIONS: Appropriate immunological and virological outcomes were seen among patients on ART for ≥9 years. However, for the complete initiating cohort, high mortality was observed, especially in the first year on ART. Concerning co-infections, tuberculosis and viral hepatitis were common among this population. Our results demonstrate that good long-term outcomes are possible even for patients with advanced AIDS at ART initiation.

Picking up the bill - improving health-care utilisation in the Democratic Republic of Congo through user fee subsidisation: a before and after study.

BACKGROUND: User fees have been shown to constitute a major barrier to the utilisation of health-care, particularly in low-income countries such as the Democratic Republic of Congo (DRC). Importantly, such barriers can lead to the exclusion of vulnerable individuals from health-care. In 2008, a donor-funded primary health-care programme began implementing user fee subsidisation in 20 health zones of the DRC. In this study, we quantified the short and long-term effects of this policy on health-care utilisation. METHODS: Sixteen health zones were included for analysis. Using routinely collected health-care utilisation data before and after policy implementation, interrupted time series regression was applied to quantify the temporal impact of the user fee policy in the studied health zones. Payment of salary supplements to health-care workers and provision of free drugs - the other components of the programme - were controlled for where possible. RESULTS: Fourteen (88%) health zones showed an immediate positive effect in health-care utilisation rates (overall median increase of 19%, interquartile range 11 to 43) one month after the policy was introduced, and the effect was significant in seven zones (P <0.05). This initial effect was sustained or increased at 24 months in five health zones but was only significant in one health zone at P <0.05. Utilisation reduced over time in the remaining health zones (overall median increase of 4%, interquartile range -10 to 33). The modelled mean health-care utilisation rate initially increased significantly from 43 consultations/1000 population to 51 consultations/1000 population during the first month following implementation (P <0.01). However, the on-going effect was not significant (P =0.69). CONCLUSIONS: Our research brings mixed findings on the effectiveness of user fee subsidisation as a strategy to increase the utilisation of services. Future work should focus on feasibility issues associated with the removal or reduction of user fees and how to sustain its effects on utilisation in the longer term.