Ecology of Aedes Mosquitoes, the Major Vectors of Arboviruses in Human Population

Aedes aegypti (Stegomyia) has been human vectors for many human diseases globally. In recent years, dengue virus has been diagnosed in different regions such as Asia and Latin America vectored by Aedes spp. mosquitoes. Dengue cases have been reported again in the several parts of African and other continental hospital. The different types of breeding sites have been found to be abundant in both urban and rural areas. The abundance of adult Ae. aegypti and habitat productivity in different settings escalates the risk of dengue transmission if viruses are found in asymptomatic population. The insecticide resistance has been found to occur in the wild population of Aedes aegypti to insecticides commonly used for indoor residual spray and long-lasting insecticidal net treatments. The control of human vector population is still a challenge as the vector has a diurnal feeding and outdoor resting behavior. Environmental management is still the best practice to be adopted in many countries for Aedes aegypti control. The currently discovered dengue vaccine might be an immediate arsenal for the community immunization

Strengthening Pharmacovigilance System to Capture Safety Data from HIV Clients on ART in Tanzania: Identification of Gaps in Safety Reporting System

In Tanzania, pharmacovigilance system is implemented by Tanzania Food and Drugs Authority (TFDA) that monitors drug use countrywide. TFDA is the main national custodian for recording, analyzing and disseminating safety information that is generated through conventional health care facilities. Since the introduction of Care and Treatment Centre (CTC) in the health care system, little has been achieved on translating safety information from these facilities to the TFDA. Since the inception of national pharmacovigilance framework in 2003 there has been no systematic operational research to map the gaps in the existing pharmacovigilance system. Furthermore, it is not clear if there is adequate training and supervision. It is, therefore, important to strengthen antiretroviral therapy (ART) related adverse drug reactions (ADRs) reporting by mapping gaps in implementation of pharmacovigilance (PV) system. Information obtained will assist in addressing training needs to ensure effective reporting of ADRs through coordinated approach involving TFDA and National AIDS Control Program (NACP) in Tanzania. A cross-sectional study was conducted in four regions (Tanga, Singida, Dodoma and Mtwara) in two PV zones. Qualitative and quantitative data collection techniques with triangulation design were used. These included; desk document review of PV recording and reporting of drug safety information; in-depth interviews with various implementation stakeholders, exit interviews with patients, in-interviews with care takers and community based organizations (CBOs) involved in the provision of care and treatment of HIV/AIDS. A total of 801 respondents participated in the quantitative data component which included; 545 exit interviews to CTC clients, 177 health service providers, 62 in-depth interviews to CTC in-charges and 17 regional and district pharmacists. Ownership of these CTCs included 83.9% government, 12.9% faith based organizations and 3.2% co-owned by the government and faith based organizations. High proportions (97.2%) of the CTC health care providers had wide knowledge on ART related ADRs. However, more than half (53.4%) of the CTC service providers had not attended any training on ART related ADRs. Among the service providers, majority (67.8%) mentioned there was no guideline in place for reporting ART related ADRs. Only, 32.1% of health care providers indicated to be aware of the tool used for collection of ART related ADRs events. Of those, 37.5% mentioned that the forms were mainly obtained from district or regional pharmacists. The ADR reports were submitted to district and regional pharmacists 48.3%, TFDA 7.0%, and NACP 7.0%. Of those who indicated to have filled and submitted ADR form, only 7.4% received feedback. The proportion of ART clients who provided information was significantly different between urban and rural in Dodoma region (p=0.002). There was variation in proportions of ART clients who had mentioned seen/heard of ART related ADR by regions and difference was significant between rural and urban for all regions except Tanga (p<0.05). Majority (47.9%) of the ART clients reported ART related ADRs to the health provider for duration ranging from 3-7 days. The qualitative results revealed that that most of the guidelines from TFDA were not known and unavailable according to most of the respondents at national level (NACP), regional, district, and at health facility level. It was surprising that one of the district pharmacists interviewed was unaware of existence of guidelines in place for ADR and PV for use in the districts. It was also found that Sometimes even when available at health facilities, there was inadequate knowledge on how to fill the ADR forms according to Key Informant at national level. Moreover, several health workers admitted that that they were not reporting ADR due to a lack of forms according to some CTC in-charges interviewed. This study has shown that despite the established PV system in Tanzania, the frequency of reporting of ART related ADRs to TFDA is low. This is due to inadequate training of health care providers on ADR reporting, shortage of staff, unavailability of TFDA ADR reporting forms and lack of regular supportive supervision. Based on these results therefore we recommend TFDA should ensure that ADR reporting forms as well as guidelines are adequately supplied and utilized at CTC level NACP should ensure sharing of safety information with TFDA and recommend dedicated focal person liable for documenting and reporting ART related ADRs recorded in CTC II patient file. Regular training, supportive supervision and feedback on ART related ADR reporting system for health care providers is needed. The financial support was provided by the Global Fund Round 8. The total budget for the project was Tsh. 69,993,000/-

Risks of Hemolysis in Glucose-6-Phosphate Dehydrogenase Deficient Infants Exposed to Chlorproguanil-Dapsone, Mefloquine and Sulfadoxine-Pyrimethamine as Part of Intermittent Presumptive Treatment of Malaria in Infants.

BACKGROUND: Chlorproguanil-dapsone (CD) has been linked to hemolysis in symptomatic glucose-6-phosphate dehydrogenase deficient (G6PDd) children. Few studies have explored the effects of G6PD status on hemolysis in children treated with Intermittent Preventive Treatment in infants (IPTi) antimalarial regimens. We sought to examine the joint effects of G6PD status and IPTi antimalarial treatment on incidence of hemolysis in asymptomatic children treated with CD, sulfadoxine-pyrimethamine (SP), and mefloquine (MQ). METHODS: A secondary analysis of data from a double-blind, placebo-controlled trial of IPTi was conducted. Hemoglobin (Hb) measurements were made at IPTi doses, regular follow-up and emergency visits. G6PD genotype was determined at 9 months looking for SNPs for the A- genotype at coding position 202. Multivariable linear and logistic regression models were used to examine hemolysis among children with valid G6PD genotyping results. Hemolysis was defined as the absolute change in Hb or as any post-dose Hb <8 g/dL. These outcomes were assessed using either a single follow-up Hb on day 7 after an IPTi dose or Hb obtained 1 to 14 or 28 days after each IPTi dose. FINDINGS: Relative to placebo, CD reduced Hb by approximately 0.5 g/dL at day 7 and within 14 days of an IPTi dose, and by 0.2 g/dL within 28 days. Adjusted declines in the CD group were larger than in the MQ and SP groups. At day 7, homo-/hemizygous genotype was associated with higher odds of Hb <8 g/dL (adjusted odds ratio = 6.7, 95% CI 1.7 to 27.0) and greater absolute reductions in Hb (-0.6 g/dL, 95% CI -1.1 to 0.003). There was no evidence to suggest increased reductions in Hb among homo-/hemizygous children treated with CD compared to placebo, SP or MQ. CONCLUSIONS: While treatment with CD demonstrated greater reductions in Hb at 7 and 14 days after an IPTi dose compared to both SP and MQ, there was no evidence that G6PD deficiency exacerbated the adverse effects of CD, despite evidence for higher hemolysis risk among G6PDd infants

Effi cacy and safety of re-treatment with the same artemisinin-based combination treatment (ACT) compared with an alternative ACT and quinine plus clindamycin after failure of fi rst-line recommended ACT (QUINACT): a bicentre, open-label, phase 3, randomised controlled trial

Background Quinine or alternative artemisinin-based combination treatment (ACT) is the recommended rescue treatment for uncomplicated malaria. However, patients are often re-treated with the same ACT though it is unclear whether this is the most suitable approach. We assessed the effi cacy and safety of re-treating malaria patients with uncomplicated failures with the same ACT used for the primary episode, compared with other rescue treatments. Methods This was a bicentre, open-label, randomised, three-arm phase 3 trial done in Lisungi health centre in DR Congo, and Kazo health centre in Uganda in 2012–14. Children aged 12–60 months with recurrent malaria infection after treatment with the fi rst-line ACT were randomly assigned to either re-treatment with the same fi rst-line ACT, an alternative ACT, which were given for 3 days, or quinine-clindamycin (QnC), which was given for 5–7 days, following a 2:2:1 ratio. Randomisation was done by computer-generated randomisation list in a block design by country. The three treatment groups were assumed to have equivalent effi cacy above 90%. Both the research team and parents or guardians were aware of treatment allocation. The primary outcome was the proportion of patients with an adequate clinical and parasitological response (ACPR) at day 28, in the per-protocol population. This trial was registered under the numbers NCT01374581 in ClinicalTrials.gov and PACTR201203000351114 in the Pan African Clinical Trials Registry. Findings From May 22, 2012, to Jan 31, 2014, 571 children were included in the trial. 240 children were randomly assigned to the re-treatment ACT group, 233 to the alternative ACT group, and 98 to the QnC group. 500 children were assessed for the primary outcome. 71 others were not included because they did not complete the follow-up or PCR genotyping result was not conclusive. The ACPR response was similar in the three groups: 91·4% (95% CI 87·5–95·2) for the re-treatment ACT, 91·3% (95% CI 87·4–95·1) for the alternative ACT, and 89·5% (95% CI 83·0–96·0) for QnC. The estimates for rates of malaria recrudescence in the three treatment groups were similar (log-rank test: χ²=0·22, p=0·894). Artemether-lumefantrine was better tolerated than QnC (p=0·0005) and artesunateamodiaquine (p<0·0001) in the modifi ed intention-to-treat analysis. No serious adverse events were observed. The most common adverse events reported in the re-treatment ACT group were anorexia (31 [13%] of 240 patients), asthenia (20 [8%]), coughing (16 [7%]), abnormal behaviour (13 [5%]), and diarrhoea (12 [5%]). Anorexia (13 [6%] of 233 patients) was the most frequently reported adverse event in the alternative ACT group. The most commonly reported adverse events in the QnC group were anorexia (12 [12%] of 98 patients), abnormal behaviour (6 [6%]), asthenia (6 [6%]), and pruritus (5 [5%]). Interpretation Re-treatment with the same ACT shows similar effi cacy as recommended rescue treatments and could be considered for rescue treatment for Plasmodium falciparum malaria. However, the eff ect of this approach on the selection of resistant strains should be monitored to ensure that re-treatment with the same ACT does not contribute to P falciparum resistance

Emerging implications of policies on malaria treatment: genetic changes in the Pfmdr-1 gene affecting susceptibility to artemether-lumefantrine and artesunate-amodiaquine in Africa.

Artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ) are the most commonly used artemisinin-based combination therapies (ACT) for treatment of Plasmodium falciparum in Africa. Both treatments remain efficacious, but single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum multidrug resistance 1 (Pfmdr1) gene may compromise sensitivity. AL and AS-AQ exert opposing selective pressures: parasites with genotype 86Y, Y184 and 1246Y are partially resistant to AS-AQ treatment, while N86, 184 F and D1246 are favoured by AL treatment. Through a systematic review, we identified 397 surveys measuring the prevalence of Pfmdr1 polymorphisms at positions 86 184 or 1246 in 30 countries in Africa. Temporal trends in SNP frequencies after introduction of AL or AS-AQ as first-line treatment were analysed in 32 locations, and selection coefficients estimated. We examined associations between antimalarial policies, consumption, transmission intensity and rate of SNP selection. 1246Y frequency decreased on average more rapidly in locations where national policy recommended AL (median selection coefficient(s) of -0.083), compared with policies of AS-AQ or both AL and AS-AQ (median s=-0.035 and 0.021, p<0.001 respectively). 86Y frequency declined markedly after ACT policy introduction, with a borderline significant trend for a more rapid decline in countries with AL policies (p=0.055). However, these trends could also be explained by a difference in initial SNP frequencies at the time of ACT introduction. There were non-significant trends for faster selection of N86 and D1246 in areas with higher AL consumption and no trend with transmission intensity. Recorded consumption of AS-AQ was low in the locations and times Pfmdr1 data were collected. SNP trends in countries with AL policies suggest a broad increase in sensitivity of parasites to AS-AQ, by 7-10 years after AL introduction. Observed rates of selection have implications for planning strategies to cycle drugs or use multiple first-line therapies to maintain drug efficacy

Supply chain management of laboratory supportive services and its potential implications on the quality of HIV diagnostic services in Tanzania

Background: Reliable supply of laboratory supportive services contributes significantly to the quality of HIV diagnostic services. This study assessed the status of supply chain management of laboratory supportive services and its potential implications on the quality of HIV diagnostic services in selected districts of Tanzania.Methods: The study was conducted in 39 health facilities (HFs) from eight districts in four regions of Tanzania, namely Iringa, Mtwara, Tabora and Tanga. Facilities with care and treatment centres for HIV/AIDS patients were purposively selected for the study. The study utilized a quantitative method of data collection. A questionnaire was administered to heads of laboratories to obtain information on laboratory supply chain management.Results:  A total of 39 health facilities (HF) were included in the study. This included 23 public and 16 private facilities. In 82% of the HFs, ordering of supplies was performed by the laboratory departments. The information commonly used to forecast requirements of the laboratories included the number of tests done (74.4%; n=29), current stock levels (69.2%; n=27), average monthly consumption (64.1%, n=25) and minimum and maximum stock levels (10.2%, n=4). Emergency orders were significantly common in public than private facilities (73.9% vs. 56.3%, p=0.004).  Delivery of ordered supplies took 1 to 180 days with a significantly longer period for public than private facilities (32.5 vs. 13.1 days, p=0.044). Most of the public HFs ordered supplies from diverse sources compared to private facilities (68.2% vs. 31.8%).Conclusion: There was a weak inventory management system and delays in delivery of supplies in the majority of HFs, which are likely to impede quality of HIV care and treatment. Strengthening capacity for data management and ensure constant supply will potentially improve the quality of HIV diagnostic services

An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples.

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed.  Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination

Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples

We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network.  It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented.  For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations.  We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent.  We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines.  Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website