Background

Rotaviruses are the most important cause of severe acute gastroenteritis worldwide in children <5 years of age. The human, G1P[8] rotavirus vaccine Rotarix™ significantly reduced severe rotavirus gastroenteritis episodes in a Phase III clinical trial conducted in infants in South Africa and Malawi. This paper examines rotavirus vaccine efficacy in preventing severe rotavirus gastroenteritis, during infancy, caused by the various G and P rotavirus types encountered during the first rotavirus-season.

Methods

Healthy infants aged 5–10 weeks were enrolled and randomized into three groups to receive either two (10 and 14 weeks) or three doses of Rotarix™ (together forming the pooled Rotarix™ group) or three doses of placebo at a 6,10,14-week schedule. Weekly home visits were conducted to identify gastroenteritis episodes. Rotaviruses were detected by ELISA and genotyped by RT-PCR and nucleotide sequencing. The percentage of infants with severe rotavirus gastroenteritis caused by the circulating G and P types from 2 weeks post-last dose until one year of age and the corresponding vaccine efficacy was calculated with 95% CI.

Results

Overall, 4939 infants were vaccinated and 4417 (pooled Rotarix™ = 2974; placebo = 1443) were included in the per protocol efficacy cohort. G1 wild-type was detected in 23 (1.6%) severe rotavirus gastroenteritis episodes from the placebo group. This was followed in order of detection by G12 (15 [1%] in placebo) and G8 types (15 [1%] in placebo). Vaccine efficacy against G1 wild-type, G12 and G8 types were 64.1% (95% CI: 29.9%; 82%), 51.5% (95% CI:-6.5%; 77.9%) and 64.4% (95% CI: 17.1%; 85.2%), respectively. Genotype P[8] was the predominant circulating P type and was detected in 38 (2.6%) severe rotavirus gastroenteritis cases in placebo group. The remaining circulating P types comprised of P[4] (20 [1.4%] in placebo) and P[6] (13 [0.9%] in placebo). Vaccine efficacy against P[8] was 59.1% (95% CI: 32.8%; 75.3%), P[4] was 70.9% (95% CI: 37.5%; 87.0%) and P[6] was 55.2% (95% CI: -6.5%; 81.3%)

Conclusions

Rotarix™ vaccine demonstrated efficacy against severe gastroenteritis caused by diverse circulating rotavirus types. These data add to a growing body of evidence supporting heterotypic protection provided by Rotarix™.

Trial registration number

NCT00241644

Objective

To assess the performance of rapid HIV antibody tests when used as part of a home-based community-wide counselling and testing strategy in northern Malawi.

Design

A cross-sectional population survey of HIV infection, 2007-2008.

Methods

Adults aged 15 or over in a demographic surveillance area were counselled and then offered an HIV test at their home by government certified counsellors. Two initial rapid tests (Detemine™ and Uni-Gold™) were performed on all samples, and a third, tie-breaker test (SD Bioline) used to resolve discordant results. All people who wanted to know were post-test counselled and informed of their results, with referral to local clinical services if found to be HIV positive. Laboratory quality control comprised re-testing all positive and every tenth negative venous blood sample collected.

Results

A total of 10819 adults provided venous blood samples for HIV-testing, of whom 7.5% (813) were HIV positive. The accuracy of the parallel testing strategy used was high, with 99.6% sensitivity, 100.0% specificity, 99.9% positive predictive value and 99.9% negative predictive values.

Conclusion

Face-to-face rapid testing by health personnel with minimum training, at the clients’ home performs well when used on a wide scale in the community setting.

Background

Treatment seeking delays among people living with HIV have adverse consequences for outcome. Gender differences in treatment outcomes have been observed in sub-Saharan Africa.

Objective

To better understand antiretroviral treatment (ART) seeking behaviour in HIV-infected adults in rural Malawi.

Methods

Qualitative interviews with male and female participants in an ART cohort study at a treatment site in rural northern Malawi triangulated with analysis of baseline clinical and demographic data for 365 individuals attending sequentially for ART screening between January 2008 and September 2009.

Results

43% of the cohort presented with late stage HIV disease classified as WHO stage 3/4. Respondents reported that women's frequency of testing, health awareness and commitment to children led to earlier ART uptake and that men's commitment to wider social networks of influence, masculine ideals of strength, and success with sexual and marital partners led them to refuse treatment until they were sick. Quantitative analysis of the screening cohort provided supporting evidence for these expressed views. Overall, male gender (adjusted OR 2.3, 95% CI1.3–3.9) and never being married (adjusted OR 4.1, 95% CI1.5–11.5) were risk factors for late presentation, whereas having ≥3 dependent children was associated with earlier presentation (adjusted OR 0.31, 95% CI0.15–0.63),compared to those with no dependent children.

Conclusion

Gender-specific barriers and facilitators operate throughout the whole process of seeking care. Further efforts to enrol men into care earlier should focus on the masculine characteristics that they value, and the risks to these of severe health decline. Our results emphasise the value of exploring as well as identifying behavioural correlates of late presentation.

Background

Drug resistance testing before initiation of, or during, antiretroviral therapy (ART) is not routinely performed in resource-limited settings. High levels of viral resistance circulating within the population will have impact on treatment programs by increasing the chances of transmission of resistant strains and treatment failure. Here, we investigate Drug Resistance Mutations (DRMs) from blood samples obtained at regular intervals from patients on ART (Baseline-22 months) in Karonga District, Malawi. One hundred and forty nine reverse transcriptase (RT) consensus sequences were obtained via nested PCR and automated sequencing from blood samples collected at three-month intervals from 75 HIV-1 subtype C infected individuals in the ART programme.

Results

Fifteen individuals showed DRMs, and in ten individuals DRMs were seen from baseline samples (reported to be ART naïve). Three individuals in whom no DRMs were observed at baseline showed the emergence of DRMs during ART exposure. Four individuals who did show DRMs at baseline showed additional DRMs at subsequent time points, while two individuals showed evidence of DRMs at baseline and either no DRMs, or different DRMs, at later timepoints. Three individuals had immune failure but none appeared to be failing clinically.

Conclusion

Despite the presence of DRMs to drugs included in the current regimen in some individuals, and immune failure in three, no signs of clinical failure were seen during this study. This cohort will continue to be monitored as part of the Karonga Prevention Study so that the long-term impact of these mutations can be assessed. Documenting proviral population is also important in monitoring the emergence of drug resistance as selective pressure provided by ART compromises the current plasma population, archived viruses can re-emerge

Background

Chronic non-communicable diseases (NCDs) are becoming significant causes of morbidity and mortality, particularly in sub-Saharan African countries, although local, high-quality data to inform evidence-based policies are lacking.

Objectives

To determine the magnitude of NCDs and their risk factors in Malawi.

Methods

Using the WHO STEPwise approach to chronic disease risk factor surveillance, a population-based, nationwide cross-sectional survey was conducted between July and September 2009 on participants aged 25–64 years. Socio-demographic and behaviour risk factors were collected in Step 1. Physical anthropometric measurements and blood pressure were documented in Step 2. Blood cholesterol and fasting blood glucose were measured in Step 3.

Results and Conclusion

A total of 5,206 adults (67% females) were surveyed. Tobacco smoking, alcohol drinking and raised blood pressure (BP) were more frequent in males than females, 25% vs 3%, 30% vs 4% and 37% vs 29%. Overweight, physical inactivity and raised cholesterol were more common in females than males, 28% vs 16%, 13% vs 6% and 11% vs 6%. Tobacco smoking was more common in rural than urban areas 11% vs 7%, and overweight and physical inactivity more common in urban than rural areas 39% vs 22% and 24% vs 9%, all with p<0.05. Overall (both sexes) prevalence of tobacco smoking, alcohol consumption, overweight and physical inactivity was 14%, 17%, 22%, 10% and prevalence of raised BP, fasting blood sugar and cholesterol was 33%, 6% and 9% respectively. These data could be useful in the formulation and advocacy of NCD policy and action plan in Malawi.

Abstract

In this preliminary study we show that in 2008, 3 years after antiretroviral therapy was introduced into the Karonga District, Malawi, a greater than expected number of drug-naive individuals have been infected with HIV-1 subtype C virus harboring major and minor drug resistance mutations (DRMs). From a sample size of 40 reverse transcriptase (RT) consensus sequences from drug-naive individuals we found five showing NRTI and four showing NNRTI mutations with one individual showing both. From 29 protease consensus sequences, again from drug-naive individuals, we found evidence of minor DRMs in three. Additional major and minor DRMs were found in clonal sequences from a number of individuals that were not present in the original consensus sequences. This clearly illustrates the importance of sequencing multiple HIV-1 variants from individuals to fully assess drug resistance.

Background

Four studies from sub-Saharan Africa have found a substantial population-level effect of ART provision on adult mortality. It is important to see if the impact changes with time since the start of treatment scale-up, and as treatment moves to smaller clinics.

Methods and Findings

During 2002-4 a demographic surveillance site (DSS) was established in Karonga district, northern Malawi. Information on births and deaths is collected monthly, with verbal autopsies conducted for all deaths; migrations are updated annually. We analysed mortality trends by comparing three time periods: pre-ART roll-out in the district (August 2002–June 2005), ART period 1 (July 2005–September 2006) when ART was available only in a town 70 km away, and ART period 2 (October 2006–September 2008), when ART was available at a clinic within the DSS area. HIV prevalence and ART uptake were estimated from a sero-survey conducted in 2007/2008. The all-cause mortality rate among 15–59 year olds was 10.2 per 1000 person-years in the pre-ART period (288 deaths/28285 person-years). It fell by 16% in ART period 1 and by 32% in ART period 2 (95% CI 18%–43%), compared with the pre-ART period. The AIDS mortality rate fell from 6.4 to 4.6 to 2.7 per 1000 person-years in the pre-ART period, period 1 and period 2 respectively (rate ratio for period 2 = 0.43, 95% CI 0.33–0.56). There was little change in non-AIDS mortality. Treatment coverage among individuals eligible to start ART was around 70% in 2008.

Conclusions

ART can have a dramatic effect on mortality in a resource-constrained setting in Africa, at least in the early years of treatment provision. Our findings support the decentralised delivery of ART from peripheral health centres with unsophisticated facilities. Continued funding to maintain and further scale-up treatment provision will bring large benefits in terms of saving lives.

Summary

Tuberculosis (TB) patients with strains common to other recent cases (‘clustering’) suggest recent transmission. HIV status and age may affect proportions clustered. We investigated TB clustering by HIV and age in a population-based study in Malawi. Among 746 patients, HIV infection increased the proportion clustered. Sex-period-adjusted odds ratios for the association of HIV and clustering were 1.26 (95% CI 0.4–4.1) for ages 15–25 years, 1.40 (0.9–2.3) for 25–50 years and 10.44 (2.3–47.9) for >50 years and remained stable over two periods examined. These results suggest that HIV increases the proportion of TB due to recent transmission in the elderly.

To assess diversity of rotavirus strains in Lilongwe, Malawi, we conducted a cross-sectional study of children with acute gastroenteritis, July 2005–June 2007. Serotype G12 was identified in 30 (5%) of 546 rotavirus-positive fecal specimens. The G12 strain possessed multiple electropherotypes and P-types, but their viral protein 7 sequences were closely related, indicating that reassortment has occurred.

Both epidemiologic and strain-related factors may contribute to large clusters of tuberculosis patients.

Tuberculosis patients with identical strains of Mycobacterium tuberculosis are described as clustered. Cluster size may depend on patient or strain characteristics. In a 7-year population-based study of tuberculosis in Karonga District, Malawi, clusters were defined by using IS6110 restriction fragment length polymorphism, excluding patterns with <5 bands. Spoligotyping was used to compare strains with an international database. Among 682 clustered patients, cluster size ranged from 2 to 37. Male patients, young adults, and town residents were over-represented in large clusters. Cluster size was not associated with HIV status or death from tuberculosis. Spoligotypes from 9 (90%) of 10 large cluster strains were identical or very similar (1 spacer different) to common spoligotypes found elsewhere, compared with 37 (66%) of 56 of those from nonclustered patients (p = 0.3). Large clusters were associated with factors likely to be related to social mixing, but spoligotypes of common strains in this setting were also common types elsewhere, consistent with strain differences in transmissibility.

Mapping distribution of lymphatic filariasis (LF) is a prerequisite for planning national elimination programmes. Results from a nation wide mapping survey for lymphatic filariasis (LF) in Malawi are presented. Thirty-five villages were sampled from 23 districts excluding three districts (Karonga, Chikwawa and Nsanje) that had already been mapped and Likoma, an Island, where access was not possible in the time frame of the survey. Antigenaemia prevalence [based on immunochromatographic card tests (ICT)] ranged from 0% to 35.9%. Villages from the western side of the country and distant from the lake tended to be of lower prevalence. The exception was a village in Mchinji district on the Malawi-Zambia border where a prevalence of 18.2% was found. In contrast villages from lake shore districts [Salima, Mangochi, Balaka and Ntcheu (Bwanje valley)] and Phalombe had prevalences of over 20%.

A national map is developed which incorporates data from surveys in Karonga, Chikwawa and Nsanje districts, carried out in 2000. There is a marked decline in prevalence with increasing altitude. Further analysis revealed a strong negative correlation (R2 = 0.7 p < 0.001) between altitude and prevalence. These results suggest that the lake shore, Phalombe plain and the lower Shire valley will be priority areas for the Malawi LF elimination programme. Implications of these findings as regards implementing a national LF elimination programme in Malawi are discussed.

A national household survey was conducted in Malawi to determine awareness and use of a socially marketed water treatment product. In all, 64% of mothers were aware of the product, and 7% were using it. Both poor and rural mothers had lower awareness and use rates. Targeting promotion to rural populations could enhance program effectiveness.

In a 7-year population-based study in Malawi, we showed that Beijing genotype tuberculosis (TB) increased as a proportion of TB cases. All the Beijing genotype strains were fully drug sensitive. Contact histories, TB type, and case-fatality rates were similar for Beijing and non-Beijing genotype TB.

To investigate the role of innate immunity in variable efficacy of Mycobacterium bovis BCG vaccination in Malawi and the United Kingdom, we examined 24-h tumor necrosis factor alpha, interleukin-1β (IL-1β), and IL-10 responses to mycobacterial purified protein derivatives (PPDs). The rank order in stimulatory potency for different PPDs was the same for all three cytokines. Before vaccination Malawians made higher pro- and anti-inflammatory responses than did United Kingdom subjects. Fewer than 5% of United Kingdom subjects made IL-10 in response to any PPD, compared to 19 to 57% responders among Malawians. Priming for regulatory IL-10 may contribute to the smaller increase in gamma interferon responses in Malawians compared to United Kingdom subjects following BCG vaccination.

Objectives

Developing countries are undergoing demographic transition with a shift from high mortality caused by communicable diseases (CD) to lower mortality rates caused by non-communicable diseases (NCD). HIV/AIDS has disrupted this trend in sub-Saharan Africa. However, in recent years, HIV-associated mortality has been reduced with the introduction of widely available antiretroviral therapy (ART). Side effects of ART may lead to increased risk of cardiovascular diseases, raising the prospects of an accelerated transition towards NCD as the primary cause of death. We report population-based data to investigate changes in cause of death owing to NCD during the first 4 years after introduction of HIV treatment.

Methods

We analysed data from a demographic surveillance system in Karonga district, Malawi, from September 2004 to August 2009. ART was introduced in mid-2005. Clinician review of verbal autopsies conducted 2–6 weeks after a death was used to establish a single principal cause of death.

Results

Over the entire period, there were 905 deaths, AIDS death rate fell from 505 to 160/100 000 person-years, and there was no evidence of an increase in NCD rates. The proportion of total deaths attributable to AIDS fell from 42% to 17% and from NCD increased from 37% to 49%.

Discussion

Our findings show that 4 years after the introduction of ART into HIV care in Karonga district, all-cause mortality has fallen dramatically, with no evidence of an increase in deaths owing to NCD.