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; Achar, Jay
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.
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.
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%).
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.
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; Lister, David; Dietrich, Sebastian; Ariti, Cono; Safaev, Hasan; Nyang'wa, Bern-Thomas; Nargiza, Parpieva; Mirzagalib, Tillashaikhov; Achar, Jay
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; Bernabeu, S; Le Pape, S; Kallala, R; Rochard, A; Verstuyft, C; Fortineau, N; Roque-Afonso, AM; Naas, T
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
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.
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.
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.
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.
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; Lon, C; D'Alessandro, U; Davis, TME; Dondorp, AM; Edstein, MD; Fairhurst, RM; Ferreira, MU; Hwang, J; Janssens, B; Karunajeewa, H; Kiechel, JR; Ladeia-Andrade, S; Laman, M; Mayxay, M; McGready, R; Moore, BR; Mueller, I; Newton, PN; Thuy-Nhien, NT; Noedl, H; Nosten, F; Phyo, AP; Poespoprodjo, JR; Saunders, DL; Smithuis, F; Spring, MD; Stepniewska, K; Suon, S; Suputtamongkol, Y; Syafruddin, D; Tran, HT; Valecha, N; Van Herp, M; Van Vugt, M; White, NJ; Guerin, PJ; Simpson, JA; Price, RN
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.
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; Kerschberger, B
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.
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.
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
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.
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
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.
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 18.104.22.168 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.
Knowledge of peri-menarcheal changes and a comparative analysis of the age at menarche among young adolescent school girls in urban and rural Cameroon
Ajong, AB; Tankala, NN; Yakum, MN; Azenoi, IS; Kenfack, B
Menarche is an expected event that occurs during the development of every normal young girl. We designed this study to evaluate the knowledge of young school girls on puberty, menarche, and menstruation, and to update data on the age at menarche in a rural and urban setting in Cameroon.
We conducted a cross-sectional survey from February to March 2017, targeting female students aged 9 to 16 years in Yaoundé (urban) and Bamougoum (rural). Participants were included using a randomised cluster sampling and data collected using an auto-administrable questionnaire. Student t-test or the Kruskal-Wallis test was used to compare means, and the odds ratio used as the measure of association between age at menarche and selected covariates.
1157 participants were included in the study; 49.3% from an urban setting and 50.7% from a rural setting. Regarding the knowledge of our participants on puberty, menarche, and menstruation, 67.20% of rural participants had good knowledge, whereas only 46.00% had good knowledge in the urban setting. Mean age at menarche was 12.76 ± 1.33 years, with the mean age at menarche in the urban setting of 12.48 ± 1.12 years and the rural setting of 13.03 ± 1.46 years. Mean age at menarche was significantly lower in participants aged below 14 years (p-value = 0.000), those with both parents alive (p-value = 0.0461), those whose fathers had skilled occupations (p-value = 0.005), those of urban resident (p-value = 0.000), and those who watched TV everyday (p-value = 0.030). Urban residence and age below 14 years were significantly associated with an earlier onset of menarche.
Rural participants had better knowledge of puberty, menarche, and the menstrual cycle than their counterparts in the urban setting. The mean age at menarche over the last two decades has dropped by 7.4 and 4.2 months per decade in urban and rural Cameroon respectively. Mean age at menarche varies significantly with age group, urban/rural residence, state of both parents (both alive/at least one dead), occupation of the father, and frequency of watching TV. Age and urban/rural residence are associated with age at onset of menarche. The continually declining age at menarche is an alarm for future early menarche-linked morbidities.
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
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.
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.
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.
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.
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