Publications

Funding for clinical research |drugs, vaccines, microbicides, diagnostics | HIV/AIDS, tuberculosis, malaria, other infectious diseases |sub-Saharan Africa

Dr Moses Masika

Kenya

EDCTP portfolio: Career Development Fellowships

Dr Moses Masika aims to determine the prevalence and genetic diversity of arboviral infections with a view to contributing to outbreak and epidemic preparedness.

Emerging and re-emerging arboviral infections

Emerging and reemerging infections are a major threat to global health today. Their occurrence is unpredictable and they often cause serious morbidity, mortality as well as economic losses. The world needs to be better prepared to handle an outbreak anytime and this requires surveillance to detect outbreaks. The challenge is to develop the tools to assess and control the threat.

The challenge

Dr Masika and his team will conduct a cross-sectional study on patients with acute febrile illness in three health facilities in the Kibera informal settlement, Nairobi city, Kenya. Sociodemographic and clinical data, as well as blood and urine samples, will be collected from 384 patients with fever for up to 5 days and no signs of localising.

Samples will be analysed using ELISA for antibodies against flaviviruses, alphaviruses and bunyaviruses. Positive samples will be further analysed using plaque reduction neutralisation assays to differentiate the specific viruses. Group-specific PCR will be done to detect any viruses from the three groups (flaviviruses, alphaviruses and bunyaviruses); Sanger sequencing will be performed on PCR-positive samples to determine the specific virus. In addition, the samples will be analysed using next-generation sequencing to detect any other viruses in the samples. Bioinformatics and phylogenetic analysis will be used to assess the genomic diversity of any arboviruses sequenced. Sociodemographic, clinical and laboratory data will be statistically analysed (SPSS).

The project

This study will determine the proportion of acute febrile illness that is due to arboviruses. Any novel or emerging viruses will also be identified and characterised. This information will help in surveillance efforts as well as the selection and development of appropriate diagnostic assays and vaccine targets for common arboviral infections in the study area and beyond.

Impact


test the safety and efficacy of this new formulation in young children

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

Emerging and reemerging infections are a major threat to global health today. Their occurrence is unpredictable and they often cause serious morbidity, mortality as well as economic losses. The world needs to be better prepared to handle an outbreak anytime and this requires surveillance to detect outbreaks. The challenge is to develop the tools to assess and control the threat.

Dr Masika and his team will conduct a cross-sectional study on patients with acute febrile illness in three health facilities in the Kibera informal settlement, Nairobi city, Kenya. Sociodemographic and clinical data, as well as blood and urine samples, will be collected from 384 patients with fever for up to 5 days and no signs of localising.

Samples will be analysed using ELISA for antibodies against flaviviruses, alphaviruses and bunyaviruses. Positive samples will be further analysed using plaque reduction neutralisation assays to differentiate the specific viruses. Group-specific PCR will be done to detect any viruses from the three groups (flaviviruses, alphaviruses and bunyaviruses); Sanger sequencing will be performed on PCR-positive samples to determine the specific virus. In addition, the samples will be analysed using next-generation sequencing to detect any other viruses in the samples. Bioinformatics and phylogenetic analysis will be used to assess the genomic diversity of any arboviruses sequenced. Sociodemographic, clinical and laboratory data will be statistically analysed (SPSS).

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

This study will determine the proportion of acute febrile illness that is due to arboviruses. Any novel or emerging viruses will also be identified and characterised. This information will help in surveillance efforts as well as the selection and development of appropriate diagnostic assays and vaccine targets for common arboviral infections in the study area and beyond.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M