This section contains articles written by MSF staff and MSF partners published in peer-reviewed journals. It contains research articles, reviews, editorials and letters. In all cases, the full text is available for free. Some articles are listed under more than one topic. The box on the right lists all the topics.

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  • Accuracy of molecular drug susceptibility testing amongst tuberculosis patients in Karakalpakstan, Uzbekistan.

    Gil, Horacio; Margaryan, Hasmik; Azamat, Ismailov; Ziba, Bekturdieva; Bayram, Halmuratov; Nazirov, Pirimqul; Gomez, Diana; Singh, Jatinder; Zayniddin, Sayfutdinov; Parpieva, Nargiza; et al. (2021-01-06)
    Objectives In this retrospective study, we evaluated the diagnostic accuracy of molecular tests (MT) for the detection of DR‐TB, compared to the gold standard liquid‐based Drug Susceptibility Testing (DST) in Karakalpakstan. Methods A total of 6,670 specimens received in the Republican TB No 1 Hospital Laboratory of Karakalpakstan between January and July 2017 from new and retreatment patients were analyzed. Samples were tested using Xpert MTB/RIF and line probe assays (LPA) for the detection of mutations associated with resistance. The sensitivity and specificity of MTs were calculated relative to results based on DST. Results The accuracy of MT for detection of rifampicin resistance was high, with sensitivity and specificity over 98%. However, we observed reduced sensitivity of LPA for detection of resistance; 86% for isoniazid (95%CI 82‐90%), 86% for fluoroquinolones (95%CI 68‐96%), 70% for capreomycin (95%CI 46‐88%) and 23% for kanamycin (95%CI 13‐35%). Conclusions We show that MTs are a useful tool for rapid and safe diagnosis of DR‐TB, however, clinicians should be aware of their limitations. Although detection of rifampicin resistance was highly accurate, our data suggests that resistance mutations circulating in the Republic of Karakalpakstan for other drugs were not detected by the methods used here. This merits further investigation.
  • Ebola-negative neonates born to Ebola-infected mothers after monoclonal antibody therapy: a case series

    Ottoni, MP; Ricciardone, JD; Nadimpalli, A; Singh, S; Katsomya, AM; Pokoso, LM; Petrucci, R (Elsevier, 2020-12-01)
    Background Few fetuses survive childbirth when the mother is positive for Ebola virus, with almost all being miscarried or stillborn, or dying shortly after birth. Before 2019, only two infants had been reported surviving past 28 days, of whom one tested positive for Ebola virus and subsequently received experimental therapies. Little is understood regarding the care of surviving neonates born to Ebola virus-positive mothers in the postnatal period and how novel anti-Ebola virus therapies might affect neonatal outcomes. Methods In this case series, we report on two neonates liveborn during the 2018–20 North Kivu Ebola epidemic in the Democratic Republic of the Congo who, along with their Ebola virus-positive mothers, received investigational monoclonal antibody treatment (mAB114 or REGN-EB3) as part of a randomised controlled trial (NCT03719586). Findings Both infants were born Ebola-negative and progressed well while in the Ebola Treatment Centre. Neither neonate developed evidence of Ebola virus disease during the course of the admission, and both were Ebola-negative at 21 days and remained healthy at discharge. Interpretation To our knowledge these neonates are the first documented as Ebola virus-negative at birth after being born to Ebola virus-positive mothers, and only the third and fourth neonates ever documented to have survived into infancy. Although no conclusions can be drawn from this small case series, and further research is required to investigate the neonatal effects of antibody therapies, these cases warrant review regarding whether post-delivery antibody therapy should be considered for all liveborn neonates of Ebola virus-positive mothers. In the context of a low resource setting, where survival of low-birthweight infants is poor, these cases also highlight the importance of adequate neonatal care.
  • Access to paediatric formulations for the treatment of childhood tuberculosis

    Nash, M; Perrin, C; Seddon, JA; Furin, J; Hauser, J; Marais, B; Kitai, I; Starke, J; McKenna, L (Elsevier, 2020-12-01)
  • Considerations for planning COVID-19 treatment services in humanitarian responses

    Garry, S; Abdelmagid, N; Baxter, L; Roberts, N; de Waroux, OL; Ismail, S; Ratnayake, R; Favas, C; Lewis, E; Checchi, F (BMC, 2020-12-01)
    The COVID-19 pandemic has the potential to cause high morbidity and mortality in crisis-affected populations. Delivering COVID-19 treatment services in crisis settings will likely entail complex trade-offs between offering services of clinical benefit and minimising risks of nosocomial infection, while allocating resources appropriately and safeguarding other essential services. This paper outlines considerations for humanitarian actors planning COVID-19 treatment services where vaccination is not yet widely available. We suggest key decision-making considerations: allocation of resources to COVID-19 treatment services and the design of clinical services should be based on community preferences, likely opportunity costs, and a clearly articulated package of care across different health system levels. Moreover, appropriate service planning requires information on the expected COVID-19 burden and the resilience of the health system. We explore COVID-19 treatment service options at the patient level (diagnosis, management, location and level of treatment) and measures to reduce nosocomial transmission (cohorting patients, protecting healthcare workers). Lastly, we propose key indicators for monitoring COVID-19 health services.
  • Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan

    du Cros, Philipp; Atadjan, Khamraev; Zinaida, Tigay; Abdrasuliev, Tleubergen; Greig, Jane; Cooke, Graham; Herboczek, Krzysztof; Pylypenko, Tanya; Berry, Catherine; Ronnachit, Amrita; et al. (European Respiratory Society (ERS), 2020-11-26)
    Background In 2016, WHO guidelines conditionally recommended standardised shorter 9–12 month regimens for multidrug-resistant tuberculosis (MDR-TB) treatment. We conducted a prospective study of a shorter standardised MDR-TB regimen in Karakalpakstan, Uzbekistan. Methods Consecutive adults and children with confirmed rifampicin-resistant pulmonary TB were enrolled between 1st September 2013 and 31st March 2015; exclusions included prior treatment with second-line anti-TB drugs, and documented resistance to ofloxacin or to two second-line injectable agents. The primary outcome was recurrence-free cure at 1 year following treatment completion. Results Of 146 enrolled, 128 patients were included: 67 female (52.3%), median age 30.1 (IQR 23.8–44.4) years. At the end of treatment, 71.9% (92/128) patients achieved treatment success, with 68% (87/128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failure with fluoroquinolone resistance amplification in 8 patients (8/22, 36.4%); 12 (9.4%) loss to follow-up; 2 (1.5%) deaths. Recurrence occurred in one patient. 14 patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (aOR 6.13, 95% CI 2.01;18.63) and adherence<95% (aOR 5.33, 95% CI 1.73;16.36) were associated with unsuccessful outcome in multivariable logistic regression. Conclusions Overall success with a standardised shorter MDR-TB regimen was moderate with considerable treatment failure and amplification of fluoroquinolone resistance. When introducing standardised shorter regimens, baseline drug susceptibility testing and minimising missed doses are critical. High rates globally of pyrazinamide, ethambutol and ethionamide resistance raise questions of continued inclusion of these drugs in shorter regimens in the absence of DST-confirmed susceptibility.
  • Evaluating Ten Commercially-Available SARS-CoV-2 Rapid Serological Tests Using the STARD (Standards for Reporting of Diagnostic Accuracy Studies) Method.

    Dortet, L; Ronat, JB; Vauloup-Fellous, C; Langendorf, C; Mendels, DA; Emeraud, C; Oueslati, S; Girlich, D; Chauvin, A; Afdjei, A; et al. (American Society for Microbiology, 2020-11-25)
    Numerous SARS-CoV-2 rapid serological tests have been developed, but their accuracy has usually been assessed using very few samples, and rigorous comparisons between these tests are scarce. In this study, we evaluated and compared 10 commercially-available SARS-CoV-2 rapid serological tests using the STARD methodology (Standards for Reporting of Diagnostic Accuracy Studies). 250 sera from 159 PCR-confirmed SARS-CoV-2 patients (collected from 0 to 32 days after onset of symptoms) were tested with rapid serological tests. Control sera (N = 254) were retrieved from pre-COVID periods from patients with other coronavirus infections (N = 11), positive rheumatoid factors (N = 3), IgG/IgM hyperglobulinemia (N = 9), malaria (n = 5), or no documented viral infection (N = 226). All samples were tested using rapid lateral flow immunoassays (LFIA) from 10 manufacturers. Only four tests achieved ≥98% specificity, with other tests ranging from 75.7%-99.2%. Sensitivities varied by the day of sample collection, from 31.7%-55.4% (Days 0-9), 65.9%-92.9% (Days 10-14), and 81.0%-95.2% (>14 days) after the onset of symptoms, respectively. Only three tests evaluated met French Health Authorities’ thresholds for SARS-CoV-2 serological tests (≥90% sensitivity + ≥98% specificity). Overall, the performances between tests varied greatly, with only a third meeting acceptable specificity and sensitivity thresholds. Knowing the analytical performance of these tests will allow clinicians and most importantly laboratorians to use them with more confidence, could help determine the general population’s immunological status, and may help to diagnose some patients with false-negative RT-PCR results.
  • Identification of main malaria vectors and their insecticide resistance profile in internally displaced and indigenous communities in Eastern Democratic Republic of the Congo (DRC).

    Loonen, Jeanine A C M; Dery, Dominic B; Musaka, Bertin Z; Bandibabone, Janvier B; Bousema, Teun; van Lenthe, Marit; Pop-Stefanija, Biserka; Fesselet, Jean-François; Koenraadt, Constantianus J M; 1 Médecins Sans Frontières (MSF), Amsterdam, The Netherlands. 2 Dépar‑ tement de Biologie, Centre de Recherche en Sciences Naturelles (CRSN/ Lwiro), Bukavu, South Kivu, Democratic Republic of the Congo. 3 Department of Medical Microbiology, Radboud Institute for Health Sciences, Radboud Uni‑ versity Medical Center, Nijmegen, The Netherlands. 4 Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Lon‑ don, UK. 5 Laboratory of Entomology, Wageningen University and Research, Wageningen, The Netherlands. (2020-11-23)
    Background Malaria remains a major public health concern in the Democratic Republic of the Congo (DRC) and its control is affected by recurrent conflicts. Médecins Sans Frontières (MSF) initiated several studies to better understand the unprecedented incidence of malaria to effectively target and implement interventions in emergency settings. The current study evaluated the main vector species involved in malaria transmission and their resistance to insecticides, with the aim to propose the most effective tools and strategies for control of local malaria vectors. Methods This study was performed in 52 households in Shamwana (Katanga, 2014), 168 households in Baraka (South Kivu, 2015) and 269 households in Kashuga (North Kivu, 2017). Anopheles vectors were collected and subjected to standardized Word Health Organization (WHO) and Center for Disease Control (CDC) insecticide susceptibility bioassays. Mosquito species determination was done using PCR and Plasmodium falciparum infection in mosquitoes was assessed by ELISA targeting circumsporozoite protein. Results Of 3517 Anopheles spp. mosquitoes collected, Anopheles gambiae sensu lato (s.l.) (29.6%) and Anopheles funestus (69.1%) were the main malaria vectors. Plasmodium falciparum infection rates for An. gambiae s.l. were 1.0, 2.1 and 13.9% for Shamwana, Baraka and Kashuga, respectively. Anopheles funestus showed positivity rates of 1.6% in Shamwana and 4.4% in Baraka. No An. funestus were collected in Kashuga. Insecticide susceptibility tests showed resistance development towards pyrethroids in all locations. Exposure to bendiocarb, malathion and pirimiphos-methyl still resulted in high mosquito mortality. Conclusions This is one of only few studies from these conflict areas in DRC to report insecticide resistance in local malaria vectors. The data suggest that current malaria prevention methods in these populations are only partially effective, and require additional tools and strategies. Importantly, the results triggered MSF to consider the selection of a new insecticide for indoor residual spraying (IRS) and a new long-lasting insecticide-treated net (LLIN). The reinforcement of correct usage of LLINs and the introduction of targeted larviciding were also included as additional vector control tools as a result of the studies.
  • Evaluating smartphone strategies for reliability, reproducibility, and quality of VIA for cervical cancer screening in the Shiselweni region of Eswatini: A cohort study

    Asgary, R; Staderini, N; Mthethwa-Hleta, S; Lopez Saavedra, PA; Garca Abrego, L; Rusch, B; Marie Luce, T; Rusike Pasipamire, L; Ndlangamandla, M; Beideck, E; et al. (Public Library of Science, 2020-11-19)
    Background Cervical cancer is among the most common preventable cancers with the highest morbidity and mortality. The World Health Organization (WHO) recommends visual inspection of the cervix with acetic acid (VIA) as cervical cancer screening strategy in resource-poor settings. However, there are barriers to the sustainability of VIA programs including declining providers’ VIA competence without mentorship and quality assurances and challenges of integration into primary healthcare. This study seeks to evaluate the impact of smartphone-based strategies in improving reliability, reproducibility, and quality of VIA in humanitarian settings. Methods and findings We implemented smartphone-based VIA that included standard VIA training, adapted refresher, and 6-month mHealth mentorship, sequentially, in the rural Shiselweni region of Eswatini. A remote expert reviewer provided diagnostic and management feedback on patients’ cervical images, which were reviewed weekly by nurses. Program’s outcomes, VIA image agreement rates, and Kappa statistic were compared before, during, and after training. From September 1, 2016 to December 31, 2018, 4,247 patients underwent screening; 247 were reviewed weekly by a VIA diagnostic expert. Of the 247, 128 (49%) were HIV–positive; mean age was 30.80 years (standard deviation [SD]: 7.74 years). Initial VIA positivity of 16% (436/2,637) after standard training gradually increased to 25.1% (293/1,168), dropped to an average of 9.7% (143/1,469) with a lowest of 7% (20/284) after refresher in 2017 (p = 0.001), increased again to an average of 9.6% (240/2,488) with a highest of 17% (17/100) before the start of mentorship, and dropped to an average of 8.3% (134/1,610) in 2018 with an average of 6.3% (37/591) after the start of mentorship (p = 0.019). Overall, 88% were eligible for and 68% received cryotherapy the same day: 10 cases were clinically suspicious for cancer; however, only 5 of those cases were confirmed using punch biopsy. Agreement rates with the expert reviewer for positive and negative cases were 100% (95% confidence interval [CI]: 79.4% to 100%) and 95.7% (95% CI: 92.2% to 97.9%), respectively, with negative predictive value (NPV) (100%), positive predictive value (PPV) (63.5%), and area under the curve of receiver operating characteristics (AUC ROC) (0.978). Kappa statistic was 0.74 (95% CI; 0.58 to 0.89); 0.64 and 0.79 at 3 and 6 months, respectively. In logistic regression, HIV and age were associated with VIA positivity (adjusted Odds Ratio [aOR]: 3.53, 95% CI: 1.10 to 11.29; p = 0.033 and aOR: 1.06, 95% CI: 1.0004 to 1.13; p = 0.048, respectively). We were unable to incorporate a control arm due to logistical constraints in routine humanitarian settings. Conclusions Our findings suggest that smartphone mentorship provided experiential learning to improve nurses’ competencies and VIA reliability and reproducibility, reduced false positive, and introduced peer-to-peer education and quality control services. Local collaboration; extending services to remote populations; decreasing unnecessary burden to screened women, providers, and tertiary centers; and capacity building through low-tech high-yield screening are promising strategies for scale-up of VIA programs.
  • The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network

    Hossain, MS; Commons, RJ; Douglas, NM; Thriemer, K; Alemayehu, BH; Amaratunga, C; Anvikar, AR; Ashley, EA; Asih, PBS; Carrara, VI; et al. (Public Library of Science, 2020-11-19)
    Background: There is a high risk of Plasmodium vivax parasitaemia following treatment of falciparum malaria. Our study aimed to quantify this risk and the associated determinants using an individual patient data meta-analysis in order to identify populations in which a policy of universal radical cure, combining artemisinin-based combination therapy (ACT) with a hypnozoitocidal antimalarial drug, would be beneficial. Methods and findings: A systematic review of Medline, Embase, Web of Science, and the Cochrane Database of Systematic Reviews identified efficacy studies of uncomplicated falciparum malaria treated with ACT that were undertaken in regions coendemic for P. vivax between 1 January 1960 and 5 January 2018. Data from eligible studies were pooled using standardised methodology. The risk of P. vivax parasitaemia at days 42 and 63 and associated risk factors were investigated by multivariable Cox regression analyses. Study quality was assessed using a tool developed by the Joanna Briggs Institute. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42018097400). In total, 42 studies enrolling 15,341 patients were included in the analysis, including 30 randomised controlled trials and 12 cohort studies. Overall, 14,146 (92.2%) patients had P. falciparum monoinfection and 1,195 (7.8%) mixed infection with P. falciparum and P. vivax. The median age was 17.0 years (interquartile range [IQR] = 9.0-29.0 years; range = 0-80 years), with 1,584 (10.3%) patients younger than 5 years. 2,711 (17.7%) patients were treated with artemether-lumefantrine (AL, 13 studies), 651 (4.2%) with artesunate-amodiaquine (AA, 6 studies), 7,340 (47.8%) with artesunate-mefloquine (AM, 25 studies), and 4,639 (30.2%) with dihydroartemisinin-piperaquine (DP, 16 studies). 14,537 patients (94.8%) were enrolled from the Asia-Pacific region, 684 (4.5%) from the Americas, and 120 (0.8%) from Africa. At day 42, the cumulative risk of vivax parasitaemia following treatment of P. falciparum was 31.1% (95% CI 28.9-33.4) after AL, 14.1% (95% CI 10.8-18.3) after AA, 7.4% (95% CI 6.7-8.1) after AM, and 4.5% (95% CI 3.9-5.3) after DP. By day 63, the risks had risen to 39.9% (95% CI 36.6-43.3), 42.4% (95% CI 34.7-51.2), 22.8% (95% CI 21.2-24.4), and 12.8% (95% CI 11.4-14.5), respectively. In multivariable analyses, the highest rate of P. vivax parasitaemia over 42 days of follow-up was in patients residing in areas of short relapse periodicity (adjusted hazard ratio [AHR] = 6.2, 95% CI 2.0-19.5; p = 0.002); patients treated with AL (AHR = 6.2, 95% CI 4.6-8.5; p < 0.001), AA (AHR = 2.3, 95% CI 1.4-3.7; p = 0.001), or AM (AHR = 1.4, 95% CI 1.0-1.9; p = 0.028) compared with DP; and patients who did not clear their initial parasitaemia within 2 days (AHR = 1.8, 95% CI 1.4-2.3; p < 0.001). The analysis was limited by heterogeneity between study populations and lack of data from very low transmission settings. Study quality was high. Conclusions: In this meta-analysis, we found a high risk of P. vivax parasitaemia after treatment of P. falciparum malaria that varied significantly between studies. These P. vivax infections are likely attributable to relapses that could be prevented with radical cure including a hypnozoitocidal agent; however, the benefits of such a novel strategy will vary considerably between geographical areas.
  • Integration of Traditional Healers in Human African Trypanosomiasis Case Finding in Central Africa: A Quasi-Experimental Study

    Kwedi Nolna, S; Ntone, R; Fouda Mbarga, N; Mbainda, S; Mutangala, W; Boua, B; Niba, M; Okoko, A (MDPI, 2020-11-17)
    Background: Based on the premise that Africans in rural areas seek health care from traditional healers, this study investigated a collaborative model between traditional healers and the national Human African Trypanosomiasis (HAT) programs across seven endemic foci in seven central African countries by measuring the model’s contribution to HAT case finding. Method: Traditional healers were recruited and trained by health professionals to identify HAT suspects based on its basics signs and symptoms and to refer them to the National Sleeping Sickness Control Program (NSSCP) for testing and confirmatory diagnosis. Results: 35 traditional healers were recruited and trained, 28 finally participated in this study (80%) and referred 278 HAT suspects, of which 20 (7.19%) were CATT positive for the disease. Most cases originated from Bandundu (45%) in the Democratic Republic of Congo and from Ngabe (35%) in Congo. Twelve (4.32%) patients had confirmatory diagnosis. Although a statistically significant difference was not shown in terms of case finding (p = 0.56), traditional healers were able to refer confirmed HAT cases that were ultimately cared for by NCSSPs. Conclusion: Integrating traditional healers in the control program of HAT will likely enhance the detection of cases, thereby, eventually contributing to the elimination of HAT in the most affected communities.
  • Evidence-based chlorination targets for household water safety in humanitarian settings: Recommendations from a multi-site study in refugee camps in South Sudan, Jordan, and Rwanda.

    Dahdaleh Institute for Global Health Research, York University, 88 The Pond Road, M3J 1P3, Toronto, Canada; Médecins sans Frontières, Plantage Middenlaan 14, 1018 DD Amsterdam, Netherlands; Development Impact Lab, University of California, Berkeley, Blum Hall #5570, Berkeley, CA, USA. Electronic address: 2Dahdaleh Institute for Global Health Research, York University, 88 The Pond Road, M3J 1P3, Toronto, Canada. 3Médecins sans Frontières, Plantage Middenlaan 14, 1018 DD Amsterdam, Netherland (2020-11-16)
    The current Sphere guideline for water chlorination in humanitarian emergencies fails to reliably ensure household water safety in refugee camps. We investigated post-distribution chlorine decay and household water safety in refugee camps in South Sudan, Jordan, and Rwanda between 2013-2015 with the goal of demonstrating an approach for generating site-specific and evidence-based chlorination targets that better ensure household water safety than the status quo Sphere guideline. In each of four field studies we conducted, we observed how water quality changed between distribution and point of consumption. We implemented a nonlinear optimization approach for the novel technical challenge of modelling post-distribution chlorine decay in order to generate estimates on what free residual chlorine (FRC) levels must be at water distribution points, in order to provide adequate FRC protection up to the point of consumption in households many hours later at each site. The site-specific FRC targets developed through this modelling approach improved the proportion of households having sufficient chlorine residual (i.e., ≥0.2 mg/L FRC) at the point of consumption in three out of four field studies (South Sudan 2013, Jordan 2014, and Rwanda 2015). These sites tended to be hotter (i.e., average mid-afternoon air temperatures >30°C) and/or had poorer water, sanitation, and hygiene (WASH) conditions, contributing to considerable chlorine decay between distribution and consumption. Our modelling approach did not work as well where chlorine decay was small in absolute terms (Jordan 2015). In such settings, which were cooler (20 to 30°C) and had better WASH conditions, we found that the upper range of the current Sphere chlorination guideline (i.e., 0.5 mg/L FRC) provided sufficient residual chlorine for ensuring household water safety up to 24 hours post-distribution. Site-specific and evidence-based chlorination targets generated from post-distribution chlorine decay modelling could help improve household water safety and public health outcomes in refugee camp settings where the current Sphere chlorination guideline does not provide adequate residual protection. Water quality monitoring in refugee/IDP camps should shift focus from distribution points to household points of consumption in order to monitor if the intended public health goal of safe water at the point of consumption is being achieved.
  • Treating HIV-associated cytomegalovirus retinitis with oral valganciclovir and intra-ocular ganciclovir by primary HIV clinicians in southern Myanmar: a retrospective analysis of routinely collected data

    Murray, J; Hilbig, A; Soe, TT; Ei, WLSS; Soe, KP; Ciglenecki, I (BMC, 2020-11-13)
    Background Cytomegalovirus retinitis (CMVR) is an opportunistic infection in HIV-infected people. Intraocular or intravenous ganciclovir was gold standard for treatment; however, oral valganciclovir replaced this in high-income countries. Low- and middle-income countries (LMIC) frequently use intraocular injection of ganciclovir (IOG) alone because of cost. Methods Retrospective review of all HIV-positive patients with CMVR from February 2013 to April 2017 at a Médecins Sans Frontièrs HIV clinic in Myanmar. Treatment was classified as local (IOG) or systemic (valganciclovir, or valganciclovir and IOG). The primary outcome was change in visual acuity (VA) post-treatment. Mortality was a secondary outcome. Results Fifty-three patients were included. Baseline VA was available for 103 (97%) patient eyes. Active CMVR was present in 72 (68%) eyes. Post-treatment, seven (13%) patients had improvement in VA, 30 (57%) had no change, and three (6%) deteriorated. Among patients receiving systemic therapy, four (12.5%) died, compared with five (24%) receiving local therapy (p = 0.19). Conclusions Our results from the first introduction of valganciclovir for CMVR in LMIC show encouraging effectiveness and safety in patients with advanced HIV. We urge HIV programmes to include valganciclovir as an essential medicine, and to include CMVR screening and treatment in the package of advanced HIV care.
  • Dengue in Western Uganda: a prospective cohort of children presenting with undifferentiated febrile illness

    Boyce, RM; Collins, M; Muhindo, R; Nakakande, R; Ciccone, EJ; Grounds, S; Espinoza, D; Zhu, Y; Matte, M; Ntaro, M; et al. (BMC, 2020-11-11)
    Background The spatial distribution and burden of dengue in sub-Saharan Africa remains highly uncertain, despite high levels of ecological suitability. The goal of this study was to describe the epidemiology of dengue among a cohort of febrile children presenting to outpatient facilities located in areas of western Uganda with differing levels of urbanicity and malaria transmission intensity. Methods Eligible children were first screened for malaria using rapid diagnostic tests. Children with a negative malaria result were tested for dengue using a combination NS1/IgM/IgG rapid test (SD Bioline Dengue Duo). Confirmatory testing by RT-PCR was performed in a subset of participants. Antigen-capture ELISA was performed to estimate seroprevalence. Results Only 6 of 1416 (0.42%) children had a positive dengue rapid test, while none of the RT-PCR results were positive. ELISA testing demonstrated reactive IgG antibodies in 28 (2.2%) participants with the highest prevalence seen at the urban site in Mbarara (19 of 392, 4.9%, p < 0.001). Conclusions Overall, these findings suggest that dengue, while present, is an uncommon cause of non-malarial, pediatric febrile illness in western Uganda. Further investigation into the eocological factors that sustain low-level transmission in urban settings are urgently needed to reduce the risk of epidemics.
  • Implementation and operational feasibility of SAMBA I HIV‐1 semi‐quantitative viral load testing at the point‐of‐care in rural settings in Malawi and Uganda

    Gueguen, M; Nicholas, S; Poulet, E; Schramm, B; Szumilin, E; Wolters, L; Wapling, J; Ajule, E; Rakesh, A; Mwenda, R; et al. (Wiley, 2020-11-07)
    Objective We monitored a large‐scale implementation of the Simple Amplification‐Based Assay semi‐quantitative viral load test for HIV‐1 version I (SAMBA I Viral Load = SAMBA I VL) within Médecins Sans Frontières’ HIV programmes in Malawi and Uganda, to assess its performance and operational feasibility. Methods Descriptive analysis of routine programme data between August 2013 and December 2016. The dataset included samples collected for VL monitoring and tested using SAMBA I VL in five HIV clinics in Malawi (four peripheral health centres and one district hospital), and one HIV clinic in a regional referral hospital in Uganda. SAMBA I VL was used for VL testing in patients who had been receiving ART for between 6 months and ten years, to determine whether plasma VL was above or below 1000 copies/mL of HIV‐1, reflecting ART failure or efficacy. Randomly selected samples were quantified with commercial VL assays. SAMBA I instruments and test performance, site throughput, and delays in communicating results to clinicians and patients were monitored. Results Between August 2013 and December 2016 a total of 60 889 patient samples were analysed with SAMBA I VL. Overall, 0.23% of initial SAMBA I VL results were invalid; this was reduced to 0.04% after repeating the test once. Global test failure, including instrument failure, was 1.34%. Concordance with reference quantitative testing of VL was 2620/2727, 96.0% (1338/1382, 96.8% in Malawi; 1282/1345, 95.3% in Uganda). For Chiradzulu peripheral health centres and Arua Hospital HIV clinic, where testing was performed on‐site, same‐day results were communicated to clinicians for between 91% and 97% of samples. Same‐day clinical review was obtained for 84.7% across the whole set of samples tested. Conclusions SAMBA I VL testing is feasible for monitoring cohorts of 1000 to 5000 ART‐experienced patients. Same‐day results can be used to inform rapid clinical decision‐making at rural and remote health facilities, potentially reducing time available for development of resistance and conceivably helping to reduce morbidity and mortality.
  • Quality, Equity and Utility of Observational Studies during 10 Years of Implementing the Structured Operational Research and Training Initiative in 72 Countries

    Zachariah, R; Rust, S; Thekkur, P; Khogali, M; Kumar, AM; Davtyan, K; Diro, E; Satyanarayana, S; Denisiuk, O; Griensven, JV; et al. (MDPI, 2020-11-06)
    Introduction: Observational studies are often inadequately reported, making it difficult to assess their validity and generalizability and judge whether they can be included in systematic reviews. We assessed the publication characteristics and quality of reporting of observational studies generated by the Structured Operational Research and Training Initiative (SORT IT). Methods: A cross-sectional analysis of original publications from SORT IT courses. SORT IT is a global partnership-based initiative aimed at building sustainable capacity for conducting operational research according to country priorities and using the generated evidence for informed decision-making to improve public health. Reporting quality was independently assessed using an adapted version of ‘Strengthening the Reporting of Observational Studies in Epidemiology’ (STROBE) checklist. Results: In 392 publications, involving 72 countries, 50 journals, 28 publishers and 24 disease domains, low- and middle-income countries (LMICs) first authorship was seen in 370 (94%) and LMIC last authorship in 214 (55%). Publications involved LMIC-LMIC collaboration in 90% and high-income-country-LMIC collaboration in 87%. The majority (89%) of publications were in immediate open access journals. A total of 346 (88.3%) publications achieved a STROBE reporting quality score of >85% (excellent), 41 (10.4%) achieved a score of 76–85% (good) and 5 (1.3%) a score of 65–75% (fair). Conclusion: The majority of publications from SORT IT adhere to STROBE guidelines, while also ensuring LMIC equity and collaborative partnerships. SORT IT is, thus, playing an important role in ensuring high-quality reporting of evidence for informed decision-making in public health.
  • Hypocalcaemia and calcium intake in pregnancy: A research protocol for critical analysis of risk factors, maternofoetal outcomes and evaluation of diagnostic methods in a third-category health facility, Cameroon

    Ajong, AB; Kenfack, B; Ali, IM; Yakum, MN; Aljerf, L; Telefo, PB (Public Library of Sciences, 2020-11-05)
    Introduction Hypocalcaemia in pregnancy remains a major health issue, particularly in the developing world where daily calcium intakes are suboptimal. This electrolyte imbalance can lead to severe maternofoetal and childhood consequences. Calcium supplementation, amongst others, contributes significantly to meeting calcium demands in pregnancy. With ionised calcaemia as the gold standard for diagnosis, total calcaemia and albumin-corrected calcaemia in other pathological states have been found to overestimate the burden of hypocalcaemia. The main objectives of this study are to describe the blood calcium level (total, albumin corrected, and ionised calcaemia) and associated maternofoetal outcomes while identifying determinants of calcium supplementation and ionised hypocalcaemia. This study will also evaluate the sensitivity and specificity of albumin corrected calcaemia as a diagnostic tool for hypocalcaemia (ionised calcaemia as the gold standard) among pregnant women in the Nkongsamba Regional Hospital, Cameroon. Methods Our study will target a total of 1067 term pregnant women who shall be included consecutively into the study as they arrive the maternity of the Nkongsamba Regional Hospital for their last antenatal care visit. Data shall be collected using a semi-structured interview-administered questionnaire and blood samples collected for total plasma calcium, albumin and serum ionized calcium assays. Additional data will be collected at birth (maternal and foetal variables; foetal outcomes evaluated as secondary outcomes). Total calcaemia and albuminemia shall be measured by atomic absorption spectrophotometry, while ionised calcaemia will be measured by ion-selective electrode potentiometry(using MSLEA15-H electrolyte analyzer) per standard BIOLABO and MSLEA15 protocols, respectively. Data will be analysed using the statistical softwares epi-Info version and STATA version 16. Expected research outcome This study will present a more precise estimate of the burden of hypocalcaemia in late pregnancy as well as identify and analyse the different factors associated with calcium supplementation and ionised hypocalcaemia among term pregnant women in a developing world setting. Maternofoetal outcomes associated with hypocalcaemia will be determined as well as the sensitivity and specificity of total and albumin-corrected calcaemia in diagnosing hypocalcaemia. Our findings will contribute significantly to designing or strengthening interventions to control this electrolyte imbalance.
  • A mixture model to assess the the immunogenicity of an oral rotavirus vaccine among healthy infants in Niger

    Hitchings, MDT; Cummings, DAT; Grais, RF; Isanaka, S (Elsevier, 2020-11-05)
    Analysis of immunogenicity data is a critical component of vaccine development, providing a biological basis to support any observed protection from vaccination. Conventional methods for analyzing immunogenicity data use either post-vaccination titer or change in titer, often defined as a binary variable using a threshold. These methods are simple to implement but can be limited especially in populations experiencing natural exposure to the pathogen. A mixture model can overcome the limitations of the conventional approaches by jointly modeling the probability of an immune response and the level of the immune marker among those who respond. We apply a mixture model to analyze the immunogenicity of an oral, pentavalent rotavirus vaccine in a cohort of children enrolled into a placebo-controlled vaccine efficacy trial in Niger. Among children with undetectable immunoglobulin A (IgA) at baseline, vaccinated children had 5.2-fold (95% credible interval (CrI) 3.7, 8.3) higher odds of having an IgA response than placebo children, but the mean log IgA among vaccinated responders was 0.9-log lower (95% CrI 0.6, 1.3) than among placebo responders. This result implies that the IgA response generated by vaccination is weaker than that generated by natural infection. Multivariate logistic regression of seroconversion defined by ≥ 3-fold rise in IgA similarly found increased seroconversion among vaccinated children, but could not demonstrate lower IgA among those who seroresponded. In addition, we found that the vaccine was less immunogenic among children with detectable IgA pre-vaccination, and that pre-vaccination infant serum IgG and mother’s breast milk IgA modified the vaccine immunogenicity. Increased maternal antibodies were associated with weaker IgA response in placebo and vaccinated children, with the association being stronger among vaccinated children. The mixture model is a powerful and flexible method for analyzing immunogenicity data and identifying modifiers of vaccine response and independent predictors of immune response.
  • Point-of-Care Approaches for Meningitis Diagnosis in a Low-Resource Setting (Southwestern Uganda): Observational Cohort Study Protocol of the “PI-POC” Trial

    Gaudenzi, G; Kumbakumba, E; Rasti, R; Nanjebe, D; Reu, P; Nyehangane, D; Martensson, A; Nassejje, M; Karlsson, J; Mzee, J; et al. (JMIR Publications, 2020-11-04)
    Background: A timely differential diagnostic is essential to identify the etiology of central nervous system (CNS) infections in children, in order to facilitate targeted treatment, manage patients, and improve clinical outcome. Objective: The Pediatric Infection-Point-of-Care (PI-POC) trial is investigating novel methods to improve and strengthen the differential diagnostics of suspected childhood CNS infections in low-income health systems such as those in Southwestern Uganda. This will be achieved by evaluating (1) a novel DNA-based diagnostic assay for CNS infections, (2) a commercially available multiplex PCR-based meningitis/encephalitis (ME) panel for clinical use in a facility-limited laboratory setting, (3) proteomics profiling of blood from children with severe CNS infection as compared to outpatient controls with fever yet not severely ill, and (4) Myxovirus resistance protein A (MxA) as a biomarker in blood for viral CNS infection. Further changes in the etiology of childhood CNS infections after the introduction of the pneumococcal conjugate vaccine against Streptococcus pneumoniae will be investigated. In addition, the carriage and invasive rate of Neisseria meningitidis will be recorded and serotyped, and the expression of its major virulence factor (polysaccharide capsule) will be investigated. Methods: The PI-POC trial is a prospective observational study of children including newborns up to 12 years of age with clinical features of CNS infection, and age-/sex-matched outpatient controls with fever yet not severely ill. Participants are recruited at 2 Pediatric clinics in Mbarara, Uganda. Cerebrospinal fluid (for cases only), blood, and nasopharyngeal (NP) swabs (for both cases and controls) sampled at both clinics are analyzed at the Epicentre Research Laboratory through gold-standard methods for CNS infection diagnosis (microscopy, biochemistry, and culture) and a commercially available ME panel for multiplex PCR analyses of the cerebrospinal fluid. An additional blood sample from cases is collected on day 3 after admission. After initial clinical analyses in Mbarara, samples will be transported to Stockholm, Sweden for (1) validation analyses of a novel nucleic acid–based POC test, (2) biomarker research, and (3) serotyping and molecular characterization of S. pneumoniae and N. meningitidis. Results: A pilot study was performed from January to April 2019. The PI-POC trial enrollment of patients begun in April 2019 and will continue until September 2020, to include up to 300 cases and controls. Preliminary results from the PI-POC study are expected by the end of 2020. Conclusions: The findings from the PI-POC study can potentially facilitate rapid etiological diagnosis of CNS infections in low-resource settings and allow for novel methods for determination of the severity of CNS infection in such environment.
  • Household air pollution and under-five mortality in sub-Saharan Africa: an analysis of 14 demographic and health surveys

    Bickton, FM; Ndeketa, L; Sibande, GT; Nkeramahame, J; Payesa, C; Milanzi, EB (BMC, 2020-11-04)
    Background Globally, over four million deaths are attributed to exposure to household air pollution (HAP) annually. Evidence of the association between exposure to HAP and under-five mortality in sub-Saharan Africa (SSA) is insufficient. We assessed the association between exposure to HAP and under-five mortality risk in 14 SSA countries. Methods We pooled Demographic and Health Survey (DHS) data from 14 SSA countries (N = 164376) collected between 2015 and 2018. We defined exposure to HAP as the use of biomass fuel for cooking in the household. Under-five mortality was defined as deaths before age five. Data were analyzed using mixed effects logistic regression models. Results Of the study population, 73% were exposed to HAP and under-five mortality was observed in 5%. HAP exposure was associated with under-five mortality, adjusted odds ratio (OR) 1.33 (95% confidence interval (CI) [1.03–1.71]). Children from households who cooked inside the home had higher risk of under-five mortality compared to households that cooked in separate buildings [0.85 (0.73–0.98)] or outside [0.75 (0.64–0.87)]. Lower risk of under-five mortality was also observed in breastfed children [0.09 (0.05-0.18)] compared to non-breastfed children. Conclusions HAP exposure may be associated with an increased risk of under-five mortality in sub-Saharan Africa. More carefully designed longitudinal studies are required to contribute to these findings. In addition, awareness campaigns on the effects of HAP exposure and interventions to reduce the use of biomass fuels are required in SSA.
  • Preparing humanitarians to address ethical problems

    McGowan, CR; Baxter, L; DuBois, M; Sheather, J; Khondaker, R; Cummings, R; Watkins, K (BMC, 2020-11-04)
    Infectious disease outbreaks represent potentially catastrophic threats to those affected by humanitarian crises. High transmissibility, crowded living conditions, widespread co-morbidities, and a lack of intensive care capacity may amplify the effects of the outbreak on already vulnerable populations and present humanitarian actors with intense ethical problems. We argue that there are significant and troubling gaps in ethical awareness at the level of humanitarian praxis. Though some ethical guidance does exist most of it is directed at public health experts and fails to speak to the day-to-day ethical challenges confronted by frontline humanitarians. In responding to infectious disease outbreaks humanitarian workers are likely to grapple with complex dilemmas opening the door to moral distress and burnout.

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