Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-15 (of 15 Records) |
Query Trace: Deus M[original query] |
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Advanced disease programming brings much needed attention and improvements to inpatient paediatric HIV care in Mozambique
Buck WC , Schindele A , Taibo E , Perez P , de Deus MIJT , Matsinhe M , Cowan J , Simione TB , Couto A . J Int AIDS Soc 2024 27 (1) e26203 In the early response to the HIV epidemic in Mozambique, paediatric antiretroviral treatment (ART) was principally available in day clinics, located in referral hospitals, with strong linkages between the inpatient wards and outpatient ART clinics. In 2013, the Ministry of Health (MoH) launched an acceleration plan that prioritized decentralization and scale‐up of ART services throughout the country [1]. The results of this effort have been remarkable with the comparison of key indicators from 2013 to 2021 demonstrating the percentage of health facilities offering ART increasing from 39% to 96%, the number of children on ART increasing from 41,400 to 99,169 and the estimated paediatric ART coverage increasing from 41% to 79% [2, 3]. | | To achieve these results, outpatient HIV care at primary health centres became the principal focus of programmatic attention, with an unintended negative impact on the quality of inpatient HIV care for children at referral hospitals. Programmatic data and local operational research demonstrated significant gaps at hospitals along the continuum of paediatric HIV care, including provider‐initiated testing and counselling (PITC), early infant diagnosis (EID) for HIV‐exposed infants, inpatient ART initiation and linkage to care post‐discharge [3, 4, 5, 6]. |
Mortality among children aged <5 years living with HIV who are receiving antiretroviral treatment - U.S. President's Emergency Plan for AIDS Relief, 28 supported countries and regions, October 2020-September 2022
Agathis NT , Faturiyele I , Agaba P , Fisher KA , Hackett S , Agyemang E , Mehta N , Kindra G , Morof DF , Mutisya I , Nyabiage L , Battey KA , Olotu E , Maphosa T , Motswere-Chirwa C , Ketlogetswe AT , Mafa-Setswalo J , Mazibuko S , de Deus MIT , Nhaguiombe HG , Machage EM , Mugisa B , Ogundehin DT , Mbelwa C , Birabwa E , Etima M , Adamu Y , Lawal I , Maswai J , Njeru D , Mwambona J , Nguhuni B , Mrina R , Hrapcak S , Siberry GK , Godfrey C , Wolf HT . MMWR Morb Mortal Wkly Rep 2023 72 (48) 1293-1299 Globally, children aged <5 years, including those living with HIV who are not receiving antiretroviral treatment (ART), experience disproportionately high mortality. Global mortality among children living with HIV aged <5 years receiving ART is not well described. This report compares mortality and related clinical measures among infants aged <1 year and children aged 1-4 years living with HIV with those among older persons aged 5-14, 15-49, and ≥50 years living with HIV receiving ART services at all clinical sites supported by the U.S. President's Emergency Plan for AIDS Relief. During October 2020-September 2022, an average of 11,980 infants aged <1 year and 105,510 children aged 1-4 years were receiving ART each quarter; among these infants and children receiving ART, 586 (4.9%) and 2,684 (2.5%), respectively, were reported to have died annually. These proportions of infants and children who died ranged from four to nine times higher in infants aged <1 year, and two to five times higher in children aged 1-4 years, than the proportions of older persons aged ≥5 years receiving ART. Compared with persons aged ≥5 years living with HIV, the proportions of children aged <5 years living with HIV who experienced interruptions in treatment were also higher, and the proportions who had a documented HIV viral load result or a suppressed viral load were lower. Prioritizing and optimizing HIV and general health services for children aged <5 years living with HIV receiving ART, including those recommended in the WHO STOP AIDS Package, might help address these disproportionately poorer outcomes. |
Cervical cancer screening positivity among women living with HIV in CDC-PEPFAR programs 2018-2022
McCormick LJ , Gutreuter S , Adeoye O , Alger SX , Amado C , Bay Z , Chirwa CM , Chituwo O , Correia D , Deus M , Dirlikov E , Efuntoye T , Gunde L , Kabaghe A , Kalamya JN , Lorenzoni C , Magesa D , Mate C , Mulokoshi T , Ninsiima JC , Nyangasi M , Nyika P , Pasipamire M , Ssali M , Tefera F , Torre LA , Urso M , Wandira R , Zemburuka B , Montandon M . J Acquir Immune Defic Syndr 2023 94 (4) 301-307 BACKGROUND: The US President's Emergency Plan for AIDS Relief (PEPFAR) aims to address the higher risk of cervical cancer among women living with HIV (WLHIV) by offering high quality screening services in the highest burden regions of the world. METHODS: We analyzed PEPFAR Monitoring, Evaluation, and Reporting data from CDC-supported sites in 13 countries in sub-Saharan Africa for WHLIV aged 15+ years who accessed cervical cancer screening services (mostly visual inspection, with ablative or excisional treatment offered for precancerous lesions), April 2018-March 2022. We calculated the positivity by age, country, and clinical visit type (first lifetime screen, or routine rescreening). We fitted negative binomial random-coefficient models of log-linear trends in time to estimate the probabilities of testing positive, and any temporal trends in positivity. RESULTS: Among the 2.8 million completed cancer screens, 5.4% identified precancerous lesions, and 0.8% were positive for suspected invasive cervical cancers (6.1% overall). The positivity rates declined over the study period among those women screening for cervical cancer for the first time, and among those women presenting to antiretroviral therapy (ART) clinics for routine rescreening. CONCLUSIONS: These positivity rates are lower than expectations set by the published literature. Further research is needed to determine if these lower rates are attributable to the high level of consistent ART use among these populations, and systematic program monitoring and quality assurance activities are essential to ensure WLHIV have access to the highest possible quality prevention services. |
Estimating the contribution of HIV-infected adults to household pneumococcal transmission in South Africa, 2016-2018: A hidden Markov modelling study (preprint)
Thindwa D , Wolter N , Pinsent A , Carrim M , Ojal J , Tempia S , Moyes J , McMorrow M , Kleynhans J , Gottberg AV , French N , Cohen C , Flasche S . medRxiv 2021 2021.05.21.21257622 Human immunodeficiency virus (HIV) infected adults are at a higher risk of pneumococcal colonisation and disease, even while receiving antiretroviral therapy (ART). To help evaluate potential indirect effects of vaccination of HIV-infected adults, we assessed whether HIV-infected adults disproportionately contribute to household transmission of pneumococci. We constructed a hidden Markov model to capture the dynamics of pneumococcal carriage acquisition and clearance observed during a longitudinal household-based nasopharyngeal swabbing study, while accounting for sample misclassifications. Households were followed-up twice weekly for 10 months for nasopharyngeal carriage detection via real-time PCR. We estimated the effect of participant’s age, HIV status, presence of a HIV-infected adult within the household and other covariates on pneumococcal acquisition and clearance probabilities. Of 1,684 individuals enrolled, 279 (16.6%) were younger children (<5 years-old) of whom 4 (1.5%) were HIV-infected and 726 (43.1%) were adults (≥18 years-old) of whom 214 (30.4%) were HIV-infected, most (173, 81.2%) with high CD4+ count. The observed range of pneumococcal carriage prevalence across visits was substantially higher in younger children (56.9-80.5%) than older children (5-17 years-old) (31.7-50.0%) or adults (11.5-23.5%). We estimate that 14.4% (95% Confidence Interval [CI]: 13.7-15.0) of pneumococcal-negative swabs were false negatives. Daily carriage acquisition probabilities among HIV-uninfected younger children were similar in households with and without HIV-infected adults (hazard ratio: 0.95, 95%CI: 0.91-1.01). Longer average carriage duration (11.4 days, 95%CI: 10.2-12.8 vs 6.0 days, 95%CI: 5.6 - 6.3) and higher median carriage density (622 genome equivalents per millilitre, 95%CI: 507-714 vs 389, 95%CI: 311.1-435.5) were estimated in HIV-infected vs HIV-uninfected adults. The use of ART and antibiotics substantially reduced carriage duration in all age groups, and acquisition rates increased with household size. Although South African HIV-infected adults on ART have longer carriage duration and density than their HIV-uninfected counterparts, they show similar patterns of pneumococcal acquisition and onward transmission.Author summary We assessed the contribution of HIV-infected adults to household pneumococcal transmission by applying a hidden Markov model to pneumococcal cohort data comprising 115,595 nasopharyngeal samples from 1,684 individuals in rural and urban settings in South Africa. We estimated 14.4% of sample misclassifications (false negatives), representing 85.6% sensitivity of a test that was used to detect pneumococcus. Pneumococcal carriage prevalence and acquisition rates, and average duration were usually higher in younger or older children than adults. The use of ART and antibiotics reduced the average carriage duration across all age and HIV groups, and carriage acquisition risks increased in larger household sizes. Despite the longer average carriage duration and higher median carriage density in HIV-infected than HIV-uninfected adults, we found similar carriage acquisition and onward transmission risks in the dual groups. These findings suggest that vaccinating HIV-infected adults on ART with PCV would reduce their risk for pneumococcal disease but may add little to the indirect protection against carriage of the rest of the population.Competing Interest StatementThe authors have declared no competing interest.Clinical TrialNCT02519803Clinical Protocols https://www.medrxiv.org/content/10.1101/2021.01.06.21249313v1.full.pdf Funding StatementThis research was commissioned by the National Institute for Health Research (NIHR) Global Health Research Unit on Mucosal Pathogens under the UK Government. PHIRST study was funded by a cooperative agreement with the United States Centers for Disease Control and Prevention (grant number 1U01IP001048) (https://www.cdc.gov) and the Bill and Melinda Gates Foundation (Grant number: OPP1164778) (https://www.gatesfoundation.org). DT, OJ are supported by th National Institute for Health Research (NIHR) Global Health Research Unit on Mucosal Pathogens (MPRU) using UK aid from the UK Government (16/136/46) (https://www.mpru.org). AP is supported by the Bill and Melinda Gates Foundation (https://www.gatesfoundation.org). SF is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant number 208812/Z/17/Z) (https://wellcome.org). CC and AvG receive grant support through their institution from Sanofi Pasteur (https://www.sanofi.com/en). The funders had no involvement in the study design; collection, analysis and interpretation of data; writing of the report; or decision to submit the article for publication.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The longitudinal pneumococcal carriage data described in this study were obtained from consenting South African children and adults as part of the PHIRST study. The use of data was granted by the University of Witwatersrand, Human Research Ethics Committee (HREC) and the Protocol Review Committee (PRC) under approval 150808, the US CDC Institutional Review Board relied on the local review (6840), and the London School of Hygiene and Tropical Medicine Observational Research Ethics Committee under approval 17902.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData cannot be shared publicly because of confidentiality. Data are available from the National Institute of Communicable Disease (NICD) if authorised by Institutional Data Access / Ethics Committee (contact via Professor Cherly Cohen, cherylc@nicd.ac.za) for researchers who meet the criteria for access to confidential data. The code underlying the results presented in the study are available from GitHub through the following link (https://github.com/deusthindwa/hmm.pneumococcus.hiv.south-africa) or contact Deus Thindwa through email: deus.thindwa@gmail.com |
HIV viral load scale-up among children and adolescents: Trends in viral load suppression, sample type and processing in 7 PEPFAR countries, 2015-2018
Hrapcak S , Pals S , Itoh M , Peters N , Carpenter D , Hackett S , Prao AK , Adje-Toure C , Eboi E , Mutisya I , Nyabiage Omoto L , Ondondo RO , Bowen N , Nyanya W , Kayira D , Kaba MD , Mwenda R , Deus MI , Almeida J , Cuco RMM , Boylan A , Beard S , Ashikoto S , van Rooyen G , Kindra G , Diallo K , Carmona S , Nazziwa E , Mwangi C , Ntale J , Ssewanyana I , Nabadda SN , Nabukenya M , Ellenberger D , Rivadeneira E . Pediatr Infect Dis J 2023 42 (4) e102-e104 HIV-positive children and adolescents face gaps in viral load (VL) testing. To understand trends in pediatric/adolescent VL testing, 7 countries collected data from Laboratory Information Management Systems. Results showed increasing proportion of VL tests done through dried blood spot (DBS) and decreased sample rejection rates for DBS compared with plasma, supporting use of DBS VL when skilled phlebotomy is unavailable. |
Effectiveness of monovalent rotavirus vaccine in Mozambique, a country with a high burden of chronic malnutrition
Chissaque A , Burke RM , Guimarães EL , Manjate F , Nhacolo A , Chilaúle J , Munlela B , Chirinda P , Langa JS , Cossa-Moiane I , Anapakala E , Bauhofer AFL , Garrine M , João ED , Sambo J , Gonçalves L , Weldegebriel G , Shaba K , Bello IM , Mwenda JM , Parashar UD , Tate JE , Mandomando I , de Deus N . Vaccines (Basel) 2022 10 (3) Mozambique introduced monovalent rotavirus vaccine (Rotarix(®)) in September 2015. We evaluated the effectiveness of Rotarix(®) under conditions of routine use in Mozambican children hospitalized with acute gastroenteritis (AGE). A test negative case-control analysis was performed on data collected during 2017-2019 from children <5 years old, admitted with AGE in seven sentinel hospital sites in Mozambique. Adjusted VE was calculated for ≥1 dose of vaccine vs. zero doses using unconditional logistic regression, where VE = (1 - aOR) × 100%. VE estimates were stratified by age group, AGE severity, malnutrition, and genotype. Among 689 children eligible for analysis, 23.7% were rotavirus positive (cases) and 76.3% were negative (controls). The adjusted VE of ≥1 dose in children aged 6-11 months was 52.0% (95% CI, -11, 79), and -24.0% (95% CI, -459, 62) among children aged 12-23 months. Estimated VE was lower in stunted than non-stunted children (14% (95% CI, -138, 66) vs. 59% (95% CI, -125, 91)). Rotavirus vaccination appeared moderately effective against rotavirus gastroenteritis hospitalization in young Mozambican children. VE point estimates were lower in older and stunted children, although confidence intervals were wide and overlapped across strata. These findings provide additional evidence for other high-mortality countries considering rotavirus vaccine introduction. |
Plasmodium falciparum kelch 13 Mutations, 9 Countries in Africa, 2014-2018.
Schmedes SE , Patel D , Dhal S , Kelley J , Svigel SS , Dimbu PR , Adeothy AL , Kahunu GM , Nkoli PM , Beavogui AH , Kariuki S , Mathanga DP , Koita O , Ishengoma D , Mohamad A , Hawela M , Moriarty LF , Samuels AM , Gutman J , Plucinski MM , Udhayakumar V , Zhou Z , Lucchi NW , Venkatesan M , Halsey ES , Talundzic E . Emerg Infect Dis 2021 27 (7) 1902-1908 The spread of drug resistance to antimalarial treatments poses a serious public health risk globally. To combat this risk, molecular surveillance of drug resistance is imperative. We report the prevalence of mutations in the Plasmodium falciparum kelch 13 propeller domain associated with partial artemisinin resistance, which we determined by using Sanger sequencing samples from patients enrolled in therapeutic efficacy studies from 9 sub-Saharan countries during 2014-2018. Of the 2,865 samples successfully sequenced before treatment (day of enrollment) and on the day of treatment failure, 29 (1.0%) samples contained 11 unique nonsynonymous mutations and 83 (2.9%) samples contained 27 unique synonymous mutations. Two samples from Kenya contained the S522C mutation, which has been associated with delayed parasite clearance; however, no samples contained validated or candidate artemisinin-resistance mutations. |
Integrated TB and HIV care for Mozambican children: temporal trends, site-level determinants of performance, and recommendations for improved TB preventive treatment
Buck WC , Nguyen H , Siapka M , Basu L , Greenberg Cowan J , De Deus MI , Gleason M , Ferreira F , Xavier C , Jose B , Muthemba C , Simione B , Kerndt P . AIDS Res Ther 2021 18 (1) 3 BACKGROUND: Pediatric tuberculosis (TB), human immunodeficiency virus (HIV), and TB-HIV co-infection are health problems with evidence-based diagnostic and treatment algorithms that can reduce morbidity and mortality. Implementation and operational barriers affect adherence to guidelines in many resource-constrained settings, negatively affecting patient outcomes. This study aimed to assess performance in the pediatric HIV and TB care cascades in Mozambique. METHODS: A retrospective analysis of routine PEPFAR site-level HIV and TB data from 2012 to 2016 was performed. Patients 0-14 years of age were included. Descriptive statistics were used to report trends in TB and HIV indicators. Linear regression was done to assess associations of site-level variables with performance in the pediatric TB and HIV care cascades using 2016 data. RESULTS: Routine HIV testing and cotrimoxazole initiation for co-infected children in the TB program were nearly optimal at 99% and 96% in 2016, respectively. Antiretroviral therapy (ART) initiation was lower at 87%, but steadily improved from 2012 to 2016. From the HIV program, TB screening at the last consultation rose steadily over the study period, reaching 82% in 2016. The percentage of newly enrolled children who received either TB treatment or isoniazid preventive treatment (IPT) also steadily improved in all provinces, but in 2016 was only at 42% nationally. Larger volume sites were significantly more likely to complete the pediatric HIV and TB care cascades in 2016 (p value range 0.05 to < 0.001). CONCLUSIONS: Mozambique has made significant strides in improving the pediatric care cascades for children with TB and HIV, but there were missed opportunities for TB diagnosis and prevention, with IPT utilization being particularly problematic. Strengthened TB/HIV programming that continues to focus on pediatric ART scale-up while improving delivery of TB preventive therapy, either with IPT or newer rifapentine-based regimens for age-eligible children, is needed. |
Immunogenicity of reduced-dose monovalent type 2 oral poliovirus vaccine in Mocuba, Mozambique
de Deus N , Capitine IPU , Bauhofer AFL , Marques S , Cassocera M , Chissaque A , Bero DM , Langa JP , Padama FM , Jeyaseelan V , Oberste MS , Estivariz CF , Verma H , Jani I , Mach O , Sutter RW . J Infect Dis 2020 226 (2) 292-298 BACKGROUND: Monovalent type 2 oral poliovirus vaccine (mOPV2) stockpile is low. One potential strategy to stretch the existing mOPV2 supply is to administer a reduced dose: one-drop instead of two-drops. METHODS: We conducted a randomized, controlled, open-label, non-inferiority trial (10% margin) to compared immunogenicity following administration of one versus two-drops of mOPV2. We enrolled 9-22-months old infants from Mocuba district of Mozambique. Poliovirus neutralizing antibodies were measured in sera collected before and one month after mOPV2 administration. Immune response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (>1:8) after vaccination or boosting titers by >4-fold for those with titers between 1:8 and 1:362 at baseline. The trial was registered at anzctr.org.au (number ACTRN12619000184178p). RESULTS: We enrolled 378 children and 262 (69%) completed per-protocol requirements. Immune response of mOPV2 was 53.6% (95% confidence interval [CI]: 44.9%-62.1%) and 60.6% (95% CI: 52.2%-68.4%) in 1-drop and 2-drops recipients, respectively. The non-inferiority margin of the 10% was not reached (difference=7.0%; 95%CI= -5.0-19.0). CONCLUSION: A small loss of immunogenicity of reduced mOPV2 was observed. Although the non-inferiority target was not achieved, the Strategic Advisory Group of Experts on Immunization, recommended the 1-drop strategy as a dose-sparing measure if mOPV2 supplies deteriorate further. |
Community-based surveys for Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions in selected regions of mainland Tanzania.
Bakari C , Jones S , Subramaniam G , Mandara CI , Chiduo MG , Rumisha S , Chacky F , Molteni F , Mandike R , Mkude S , Njau R , Herman C , Nace DP , Mohamed A , Udhayakumar V , Kibet CK , Nyanjom SG , Rogier E , Ishengoma DS . Malar J 2020 19 (1) 391 BACKGROUND: Histidine-rich protein 2 (HRP2)-based malaria rapid diagnostic tests (RDTs) are effective and widely used for the detection of wild-type Plasmodium falciparum infections. Although recent studies have reported false negative HRP2 RDT results due to pfhrp2 and pfhrp3 gene deletions in different countries, there is a paucity of data on the deletions of these genes in Tanzania. METHODS: A community-based cross-sectional survey was conducted between July and November 2017 in four regions: Geita, Kigoma, Mtwara and Ruvuma. All participants had microscopy and RDT performed in the field and provided a blood sample for laboratory multiplex antigen detection (for Plasmodium lactate dehydrogenase, aldolase, and P. falciparum HRP2). Samples showing RDT false negativity or aberrant relationship of HRP2 to pan-Plasmodium antigens were genotyped to detect the presence/absence of pfhrp2/3 genes. RESULTS: Of all samples screened by the multiplex antigen assay (n = 7543), 2417 (32.0%) were positive for any Plasmodium antigens while 5126 (68.0%) were negative for all antigens. The vast majority of the antigen positive samples contained HRP2 (2411, 99.8%), but 6 (0.2%) had only pLDH and/or aldolase without HRP2. Overall, 13 samples had an atypical relationship between a pan-Plasmodium antigen and HRP2, but were positive by PCR. An additional 16 samples with negative HRP2 RDT results but P. falciparum positive by microscopy were also chosen for pfhrp2/3 genotyping. The summation of false negative RDT results and laboratory antigen results provided 35 total samples with confirmed P. falciparum DNA for pfhrp2/3 genotyping. Of the 35 samples, 4 (11.4%) failed to consistently amplify positive control genes; pfmsp1 and pfmsp2 and were excluded from the analysis. The pfhrp2 and pfhrp3 genes were successfully amplified in the remaining 31 (88.6%) samples, confirming an absence of deletions in these genes. CONCLUSIONS: This study provides evidence that P. falciparum parasites in the study area have no deletions of both pfhrp2 and pfhrp3 genes. Although single gene deletions could have been missed by the multiplex antigen assay, the findings support the continued use of HRP2-based RDTs in Tanzania for routine malaria diagnosis. There is a need for the surveillance to monitor the status of pfhrp2 and/or pfhrp3 deletions in the future. |
The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC.
Verity R , Aydemir O , Brazeau NF , Watson OJ , Hathaway NJ , Mwandagalirwa MK , Marsh PW , Thwai K , Fulton T , Denton M , Morgan AP , Parr JB , Tumwebaze PK , Conrad M , Rosenthal PJ , Ishengoma DS , Ngondi J , Gutman J , Mulenga M , Norris DE , Moss WJ , Mensah BA , Myers-Hansen JL , Ghansah A , Tshefu AK , Ghani AC , Meshnick SR , Bailey JA , Juliano JJ . Nat Commun 2020 11 (1) 2107 The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a high-throughput genotyping tool. We identify an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identify highly related parasites over large geographic distances, indicative of gene flow and migration. Our results are consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations. |
Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated malaria and prevalence of Pfk13 and Pfmdr1 polymorphisms after a decade of using artemisinin-based combination therapy in mainland Tanzania.
Ishengoma DS , Mandara CI , Francis F , Talundzic E , Lucchi NW , Ngasala B , Kabanywanyi AM , Mahende MK , Kamugisha E , Kavishe RA , Muro F , Mohamed A , Mandike R , Mkude S , Chacky F , Paxton L , Greer G , Kitojo CA , Njau R , Martin T , Venkatesan M , Warsame M , Halsey ES , Udhayakumar V . Malar J 2019 18 (1) 88 BACKGROUND: The World Health Organization recommends regular therapeutic efficacy studies (TES) to monitor the performance of first and second-line anti-malarials. In 2016, efficacy and safety of artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria were assessed through a TES conducted between April and October 2016 at four sentinel sites of Kibaha, Mkuzi, Mlimba, and Ujiji in Tanzania. The study also assessed molecular markers of artemisinin and lumefantrine (partner drug) resistance. METHODS: Eligible patients were enrolled at the four sites, treated with standard doses of AL, and monitored for 28 days with clinical and laboratory assessments. The main outcomes were PCR corrected cure rates, day 3 positivity rates, safety of AL, and prevalence of single nucleotide polymorphisms in Plasmodium falciparum kelch 13 (Pfk13) (codon positions: 440-600) and P. falciparum multi-drug resistance 1 (Pfmdr1) genes (codons: N86Y, Y184F and D1246Y), markers of artemisinin and lumefantrine resistance, respectively. RESULTS: Of 344 patients enrolled, three withdrew, six were lost to follow-up; and results were analysed for 335 (97.4%) patients. Two patients had treatment failure (one early treatment failure and one recrudescent infection) after PCR correction, yielding an adequate clinical and parasitological response of > 98%. Day 3 positivity rates ranged from 0 to 5.7%. Common adverse events included cough, abdominal pain, vomiting, and diarrhoea. Two patients had serious adverse events; one died after the first dose of AL and another required hospitalization after the second dose of AL (on day 0) but recovered completely. Of 344 samples collected at enrolment (day 0), 92.7% and 100% were successfully sequenced for Pfk13 and Pfmdr1 genes, respectively. Six (1.9%) had non-synonymous mutations in Pfk13, none of which had been previously associated with artemisinin resistance. For Pfmdr1, the NFD haplotype (codons N86, 184F and D1246) was detected in 134 (39.0%) samples; ranging from 33.0% in Mlimba to 45.5% at Mkuzi. The difference among the four sites was not significant (p = 0.578). All samples had a single copy of the Pfmdr1 gene. CONCLUSION: The study indicated high efficacy of AL and the safety profile was consistent with previous reports. There were no known artemisinin-resistance Pfk13 mutations, but there was a high prevalence of a Pfmdr1 haplotype associated with reduced sensitivity to lumefantrine (but no reduced efficacy was observed in the subjects). Continued TES and monitoring of markers of resistance to artemisinin and partner drugs is critical for early detection of resistant parasites and to inform evidence-based malaria treatment policies. Trial Registration ClinicalTrials.gov NCT03387631. |
Early impact of rotavirus vaccination in children less than five years of age in Mozambique
de Deus N , Chilaule JJ , Cassocera M , Bambo M , Langa JS , Sitoe E , Chissaque A , Anapakala E , Sambo J , Guimaraes EL , Bero DM , Joao ED , Cossa-Moiane I , Mwenda JM , Weldegebriel GG , Parashar UD , Tate JE . Vaccine 2017 36 (47) 7205-7209 BACKGROUND: Mozambique introduced rotavirus vaccine (Rotarix, GSK Biologicals) in the National Immunization Program in September 2015 with the objective of reducing the burden of total diarrheal disease and specifically severe rotavirus disease. This study aimed to evaluate the early impact of rotavirus vaccine in reducing all-cause diarrhea and rotavirus-specific hospitalizations. METHODS: We analysed stool specimens collected from children under five years old, between January 2014 and June 2017 within the National Surveillance for Acute Diarrhea. We compared annual changes in rotavirus positivity, median age of children hospitalized for rotavirus and the number of all-cause for diarrheal hospitalizations. Rotavirus detection was performed using enzyme immunoassay. RESULTS: During this period, 1296 samples were collected and analyzed. Rotavirus positivity before vaccine introduction was 40.2% (39/97) in 2014 and 38.3% (225/588) in 2015, then after vaccine introduction reduced to 12.2% and 13.5% in 2016 and 2017, respectively. The median age of children hospitalized for rotavirus was 9 and 11 months in 2014 and 2015 and 10 months in 2016 and 2017. Rotavirus hospitalizations exhibited a seasonal peak prior to vaccine introduction, between June and September in 2014 and 2015, coinciding with winter period in Mozambique. After vaccine introduction, the peak was delayed until August to December in 2016 and was substantially diminished. There was a reduction in all-cause acute diarrhea hospitalizations in children aged 0-11 months after vaccine introduction. CONCLUSION: We observed a reduction in rotavirus positivity and in the number of all-cause diarrhea hospitalizations after vaccine introduction. The data suggest rotavirus vaccine is having a positive impact on the control of rotavirus diarrheal disease in Mozambique. |
Surveillance for sulfadoxine-pyrimethamine resistant malaria parasites in the Lake and Southern Zones, Tanzania, using pooling and next-generation sequencing.
Ngondi JM , Ishengoma DS , Doctor SM , Thwai KL , Keeler C , Mkude S , Munishi OM , Willilo RA , Lalji S , Kaspar N , Kitojo C , Paxton LA , Hathaway NJ , Bailey JA , Juliano JJ , Meshnick SR , Gutman J . Malar J 2017 16 (1) 236 BACKGROUND: Malaria in pregnancy (MiP) remains a major public health challenge in areas of high malaria transmission. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended to prevent the adverse consequences of MiP. The effectiveness of SP for IPTp may be reduced in areas where the dhps581 mutation (a key marker of high level SP resistance) is found; this mutation was previously reported to be common in the Tanga Region of northern Tanzania, but there are limited data from other areas. The frequency of molecular markers of SP resistance was investigated in malaria parasites from febrile patients at health centres (HC) in seven regions comprising the Lake and Southern Zones of mainland Tanzania as part of the ongoing efforts to generate national-wide data of SP resistance. METHODS: A cross-sectional survey was conducted in the outpatient departments of 14 HCs in seven regions from April to June, 2015. 1750 dried blood spot (DBS) samples were collected (117 to 160 per facility) from consenting patients with positive rapid diagnostic tests for malaria, and no recent (within past 2 months) exposure to SP or related drugs. DNA was extracted from the DBS, pooled by HC, and underwent pooled targeted amplicon deep sequencing to yield estimates of mutated parasite allele frequency at each locus of interest. RESULTS: The dhps540 mutation was common across all 14 sites, ranging from 55 to 98.4% of sequences obtained. Frequency of the dhps581 mutation ranged from 0 to 2.4%, except at Kayanga HC (Kagera Region, Lake Zone) where 24.9% of sequences obtained were mutated. The dhfr164 mutation was detected only at Kanyanga HC (0.06%). CONCLUSION: By pooling DNA extracts, the allele frequency of mutations in 14 sites could be directly determined on a single deep-sequencing run. The dhps540 mutant was very common at all locations. Surprisingly, the dhps581 was common at one health center, but rare in all the others, suggesting that there is geographic micro-heterogeneity in mutant distribution and that accurate surveillance requires inclusion of multiple sites. A better understanding of the effect of the dhps581 mutant on the efficacy of IPTp-SP is needed. |
Development of a multiplexed polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay to identify common members of the subgenera Culex (Culex) and Culex (Phenacomyia) in Guatemala
Kent RJ , Deus S , Williams M , Savage HM . Am J Trop Med Hyg 2010 83 (2) 285-91 Morphological differentiation of mosquitoes in the subgenera Culex (Culex) and Culex (Phenacomyia) in Guatemala is difficult, with reliable identification ensured only through examination of larval skins from individually reared specimens and associated male genitalia. We developed a multiplexed polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay to identify common Cx. (Cux.) and Cx. (Phc.). Culex (Cux.) chidesteri, Cx. (Cux.) coronator, Cx. (Cux.) interrogator, Cx. (Cux.) quinquefasciatus, Cx. (Cux.) nigripalpus/Cx. (Cux.) thriambus, and Cx. (Phc.) lactator were identified directly with a multiplexed primer cocktail comprising a conserved forward primer and specific reverse primers targeting ribosomal DNA (rDNA). Culex nigripalpus and Cx. thriambus were differentiated by restriction digest of homologous amplicons. The assay was developed and optimized using well-characterized specimens from Guatemala and the United States and field tested with unknown material from Guatemala. This assay will be a valuable tool for mosquito identification in entomological and arbovirus ecology studies in Guatemala. |
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