Transmission reduction in HIV, TB and Malaria

  • This Programme will take advantage of established methodology, carefully mapped populations, community based interventions and innovative technology to understand and interrupt transmission of HIV, TB and malaria in Malawi. The methods described will be generalizable to the region.
  • Malawi has a HIV sero-prevalence of 11%; an excellent ART roll-out has now occurred therefore HIV transmission reduction is the urgent priority. Landmark work in MLW has recently occurred in 2 areas. First, self-testing has redefined the sociological context in which HIV diagnosis occurs and has created the potential for radical change in transmission dynamics. In the event of early testing, high community awareness and good community access to drugs, the number of new cases resulting from any index case can be dramatically reduced. This work is led by Corbett whose thinking in this area has shifted policy across southern Africa (UNITAID $15m). Second, Mwandumba and Jambo (WT Intermediate Fellowship on HIV persistence) have defined infectious HIV virus at single cell level, many orders of magnitude below the sensitivity of viral load detection. This work allows (a) planning of treatment trials aiming for much lower levels of infection, (b) detection of compartment reservoirs of infection and (c) revision of antiviral therapy long before detectable viral load, with further immunological damage, has been allowed to occur.
  • The National TB Programme (NTP) in Malawi is excellent in terms of organisation and effectiveness and has a pro-research leadership. Despite the enormous pressure exerted by the HIV pandemic, the Malawi NTP has now been selected as one of 6 global exemplar countries in the End TB programme of the WHO. This success is underpinned by the MLW Group led by Corbett. Since demonstrating reduction in TB transmission by community testing and treating in Zimbabwe, she has developed geospatial mapping and community testing in TB prevention to a level never previously achieved. Subtle effects (community sensitisation to symptoms and hence increased health care seeking) have now been described with great precision. Target populations can now therefore be identified for selective intervention (e.g. gender based differences in care seeking, gatherings with exposure risk such as church). 
    Further, the MLW Mucosal Immunology Group (Mwandumba/Jambo) have described incomplete restoration of anti-TB immunity in HIV-infected patients on ART. This work supports findings of clinical trials from Botswana and SA which showed significant reduction in TB incidence and mortality in HIV-infected individuals who started ART and INH prophylaxis together and continued for 3yrs. The Malawi NTP is now planning to implement INH prophylaxis in HIV-infected patients starting ART in 5 districts.
  • Malawi reached its MDG target reduction in child mortality, and cases of cerebral malaria admission in Blantyre have declined drastically. Reductions have in part been attributed to the scaling-up of insecticide treated bed nets, introduction of highly effective artemisinin combination therapy for uncomplicated malaria and improved diagnostics. MLW led in many of these studies and will now focus on why current proven interventions have not had even greater impact (collaboration partner in NIH ICEMR), the effect of parasite burden reduction on development and maintenance of host immunity in the population (Mandala collaboration WTCMP Glasgow), determinants or meaningful correlates of protective immunity (collaboration Rogerson –previous WT Int Fellow Blantyre) and how successful reduction in burden of disease alters parasite population biology (Nkhoma Intermediate Fellowship). 

    The 2016-2030 global strategy for transmission reduction requires affordable targeted intervention packages that overcome natural heterogeneity in transmission. In Chikhwawa, Terlouw and Diggle have developed novel surveillance methodologies for affordable fine-scale mapping. The application of these methods in Chikhwawa has opened up opportunities to combine geospatial, genomic and immunological data and understand how transmission from subclinical infections contributes to clinical malaria as well as the molecular and biochemical basis of parasite resistance to drugs both in current clinical use and those at an advanced stage of the developmental pipeline (Terlouw). 

    Anticipating an increasing role of antimalarial drugs in transmission reduction efforts, Mwapasa and Terlouw used an EDCTP funded programme of PKPD dose-optimization in vulnerable subgroups to define treatment guidelines of DHA-PPQ, the main candidate drug for mass drug administration in southern and eastern Africa (adopted WHO). They have established a joint MLW/COM Pharmacology laboratory that reached WWARN accreditation for all the main antimalarial drugs, the only such laboratory in the Southern African region outside Cape Town.
    1. Determine the impact of HIV self-testing on behaviour, transmission and rates of infection
    2. Community intervention leading to measureable reduction in TB transmission
    3. Determine viable national approaches to use fine-scale methods to map and predict malaria heterogeneity. Based on this determine the impact of targeted malaria intervention packages on transmission and disease burden reduction
    4. Development of senior Malawian scientists Mwandumba, Jambo, Mandala Nkhoma and Nyondo-Mipando.
    5. Recruit a senior Clinical Epidemiologist and Vector Biologist to the Programme.