Community localities for Clinical Intervention Trials of LLINs/IRS

Two localities have been surveyed and prepared for Phase 3 evaluations, Bondo and Msitu wa Tembo. Msitu wa Tembo is a hyperendemic semi-arid area inland area with an entomological inoculation rate (EIR) of 0-10. Bondo is located near the coastal belt and has high humidity and is hypoendemic for malaria transmission.

Figure 1. Hamlet census information from the central village office. Typical rural housing in this area with mud walls and palm or grass thatch roof.

Trials with clinical outcome measures will be conducted in villages surrounding Bondo in Handeni District, a lowland area (250-350m asl) of Tanga region in north-eastern Tanzania. This area is predominantly occupied by subsistence farmers, with oranges being produced seasonally as cash crops

Malaria transmission is intense and perennial, and due to a mixed vector population of Anopheles gambiae s.s., An. funestus, and An. arabiensis (Caroline Maxwell, personal communication, 2008; White 1972).

A mixed vector population will allow us to assess differential effectiveness of IRS/LLIN combinations against all 3 major African vectors. Reports from Western Kenya suggest that high LLIN coverage has resulted in altered species dynamics with An. arabiensis becoming the dominant species over An. gambiae s.s (Gimnig J, pers. communication, 2009).

Figure 2. Number marking of doors for baseline data collection

The area is rural with villages situated along a dead-end, unpaved road to the east of Michungwani town (GPS coordinates: 05°20’25.55″ S; 38° 33′ 10.75″ E). Access to health-care was limited in this area with the nearest health care facility in Segera town (05°19’28.32″ S; 38°32’36.96″ E) until a research clinic at a central location in the study area (Bondo village) was constructed in 2008. Previous malaria macronutrient studies conducted in this area with Kilimanjaro Christian Medical College were done between 5 February 2008 and 12 March 2009. During this study virtually all infections were due to Plasmodium falciparum. The incidence of uncomplicated episodes (first events and all events) was 2.93 (=507/172.8 child-years) and 2.98 (=1578/528.7 child-years) (figure 1), where malaria was defined as follows:

- Reported and confirmed fever (axillary temperature >= 37.5°C) plus a positive result for a pLDH-dipstick test, OR:
- Reported fever with inflammation (whole blood C-reactive protein concentration >10 mg/L) plus a positive result for a pLDH-dipstick test (Veenemans et al, unpublished 2009).

- Reported and confirmed fever (axillary temperature >= 37.5°C) plus a positive result for a pLDH-dipstick test, OR:
- Reported fever with inflammation (whole blood C-reactive protein concentration >10 mg/L) plus a positive result for a pLDH-dipstick test (Veenemans et al, unpublished 2009).

Figure 3. Showing malaria incidence over time in a cohort of Tanzanian children aged 6-60 months. Intense peak in malaria transmission recorded after onset of the short rains.

Figure 4. Individual burden of malaria. Showing number of malaria episodes per child (x-axis) and frequency (y-axis) (Veenemans et al, unpublished 2009)

LLIN use in the region has increased steadily through the Tanzania National Voucher Scheme (TNVS) for pregnant mothers and the Under Five Coverage Campaign (U5CC) (PMI, 2009). Recent household surveys showed that in rural villages 71% of under 5′s slept under a net compared with 57% of >5′s This proportion falls to 54% and 33% when only insecticide treated nets are considered (Bernard et al. 2009).

GPS mapping of all structures in the area is underway, afterwhich suitable village clusters will be divided in preparation for Phase 3 community studies of IRS or LLINs. Entomlogical monitoring is being undertaken through use of CDC light traps and larval sampling. This is being done to monitor seasonal fluctuations in mosquito densities as well as to speciate the Anopheles mosquitoes captured.

Figure 5. Technician preparing blood slides from patients to be checked for malaria parasites. Field entomologists carrying out daily trapping of mosquitoes from village houses.

Figures 6. Larval collections of Anopheles mosquitoes made during the dry season in semi-permanent breeding sites. Children of Bondo welcome KCM College/LSHTM PhD student.

Early work in the area by White (1971) suggested that both An. arabiensis and An. gambiae s.s. are present with interesting seasonal dynamics. It appears that An. arabiensis may be the dominant species during the dry season, with An. gambiae populations peaking during the rainy seasons. If this is confirmed the area will be particularly useful to compare the effects of an insecticide treatment against 2 malaria vectors with quite different behavioural characteristics.

Msitu wa Tembo is situated in Lower Moshi (Latiude 3° 33′S; – Longitude 37° 17′ E), altitude 714m, located between Masai Savannah and the foothills of Kilimanjaro. Average annual rainfall is 615mm with 70% falling between March-May.

This area is hyperendemic for malaria transmission with an EIR of 0-10 infective bites per year. In 2004 130 episodes of malaria were recorded from a population of 3,388 individuals. All structures in the area have been mapped using GIS. Anopheline mosquitoes trapped in the area were An. arabiensis, with mosquito population and malaria transmission peaks coinciding after the rainy season (figure 7). Recent resistance testing has shown An. arabiensis in Msitu wa Tembo are resistant to pyrethroids (Matowo et al., in press) but not to DDT. This coupled with studies of resistance mechanisms in other parts of Lower Moshi suggest the mechanism of resistance to be metabolic and not KDR.

Figure 7numbers of mosquito and patients during 2004

Rainfall, numbers of mosquito and patients during 2004. Bars indicate the total rainfall per week collected in 21 rain gauges at the nearby sugar plantation (left hand y-axis). The solid line indicates the total proportion of female Anopheles mosquitoes caught per week (left hand y-axis). The broken line the total number of malaria cases seen by the health centre per week (right hand Y-axis).