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author:("Ngwira, bagre")
1.  Morbidity and mortality in HIV-exposed under-five children in a rural Malawi setting: a cohort study 
Journal of the International AIDS Society  2014;17(4Suppl 3):19696.
Introduction
Paediatric HIV infection significantly contributes to child morbidity and mortality in southern Africa. In Malawi as in most countries in the region, care of HIV-exposed children is constrained by the lack of area-specific information on their risk to dying and morbidity. This research estimates and compares morbidity and mortality events between HIV-exposed and -unexposed under-five children in a rural Malawian setting.
Methods
Data for children under the age of five collected from January 2009 to June 2011 at a demographic and health site in Karonga district of northern Malawi were analyzed. Morbidity and mortality rates among HIV-exposed and -unexposed children were calculated and compared using Kaplan-Meier survival analysis and Cox proportional hazard regression.
Results
Overall (n=7,929) cohort data of under-five children born in a demographic and health site represented 12380.8 person years of observation (PYO) of which 3.1% were contributed by HIV-exposed infants. Females accounted for half of the sample, and the overall mean age was 18.4 months (SD 13.4) with older children in the HIV–unexposed group. All-cause morbidity rate was 337.6/1000 PYO (95% CI 327.5/1000–348.0/1000) and HIV-exposed children morbidity rate was 1.34 times higher (p<0.001) compared to HIV-unexposed children. integrated management of childhood illness (IMCI) pneumonia was the most common diagnosis (39.3%) in this cohort. Child mortality rate was 16.6/1000 PYO (95% CI 14.5–19.1) from 206 deaths. HIV-exposed children had 4.5 times higher (p<0.001) mortality rate compared to the HIV-unexposed children. Higher mortality rates were observed in children under one year (129.2/1000 PYO) compared to older age groups.
Conclusion
HIV exposure at birth has a greater impact on child morbidity and mortality especially in the first year of life. This underscores the need for targeted and synergetic interventions that included focused prevention of mother-to-child transmission (PMTCT) which could reduce HIV transmission to children in their infancy in this setting.
doi:10.7448/IAS.17.4.19696
PMCID: PMC4225439  PMID: 25397446
2.  Efficacy of human rotavirus vaccine against severe gastroenteritis in Malawian children in the first two years of life: a randomised, double-blind, placebo controlled trial 
Vaccine  2012;30(0 1):A36-A43.
Rotavirus gastroenteritis is a major cause of morbidity and mortality among African infants and young children. A phase III, placebo-controlled, multi-centre clinical trial of a live, oral G1P[8] human rotavirus vaccine (RIX4414) undertaken in Malawi and South Africa significantly reduced the incidence of severe rotavirus gastroenteritis in the first year of life. We now report on vaccine efficacy in the Malawi cohort of children who were followed into the second year of life. A total of 1,773 healthy infants were enrolled in Blantyre, Malawi into three groups. Two groups received three doses of RIX4414 or placebo at age 6, 10, and 14 weeks and the third group received placebo at 6 weeks and RIX4414 at age 10 and 14 weeks. Subjects were followed by weekly home visits for episodes of gastroenteritis until 1 year of age, and were then re-consented for further follow-up to 18-24 months of age. Severity of gastroenteritis episodes was graded according to the Vesikari scoring system. Seroconversion for anti-rotavirus IgA was determined on a subset of children by using ELISA on pre- and post-vaccine blood samples. Rotavirus VP7 (G) and VP4 (P) genotypes were determined by RT-PCR. A total of 70/1030 (6.8%, 95% CI 5.3 - 8.5) subjects in the pooled (2 dose plus 3 dose) RIX4414 group compared with 53/483 (11.0%, 8.3 – 14.1) subjects in the placebo group developed severe rotavirus gastroenteritis in the entire follow-up period (Vaccine Efficacy 38.1% (9.8 – 57.3). The point estimate of efficacy in the second year of life (17.6%; −59.2 – 56.0) was lower than in the first year of life (49.4%; 19.2 – 68.3). There were non-significant trends towards a higher efficacy in the second year of life among children who received the three-dose schedule compared with the two-dose schedule, and a higher anti-rotavirus IgA seroresponse rate in the three-dose RIX4414 group. Rotavirus strains detected included genotype G12 (31%); G9 (23%); and G8 (18%); only 18% of strains belonged to the G1P[8] genotype. While the optimal dosing schedule of RIX4414 in African infants requires further investigation, vaccination with RIX4414 significantly reduced the incidence of severe gastroenteritis caused by diverse rotavirus strains in an impoverished African population with high rotavirus disease burden in the first two years of life.
doi:10.1016/j.vaccine.2011.09.120
PMCID: PMC3982044  PMID: 22520135
Gastroenteritis; Rotavirus; Vaccine; Genotypes
3.  Molecular characterization of rotavirus strains detected during a clinical trial of a human rotavirus vaccine in Blantyre, Malawi 
Vaccine  2012;30(0 1):A140-A151.
The human, G1P[8] rotavirus vaccine (Rotarix) significantly reduced severe rotavirus gastroenteritis episodes in a clinical trial in South Africa and Malawi, but vaccine efficacy was lower in Malawi (49.5%) than reported in South Africa (76.9%) and elsewhere. The aim of this study was to examine the molecular relationships of circulating wild-type rotaviruses detected during the clinical trial in Malawi to RIX4414 (the strain contained in Rotarix) and to common human rotavirus strains. Of 88 rotavirus-positive, diarrhoeal stool specimens, 43 rotaviruses exhibited identifiable RNA migration patterns when examined by polyacrylamide gel electrophoresis. The genes encoding VP7, VP4, VP6 and NSP4 of 5 representative strains possessing genotypes G12P[6], G1P[8], G9P[8], and G8P[4] were sequenced. While their VP7 (G) and VP4 (P) genotype designations were confirmed, the VP6 (I) and NSP4 (E) genotypes were either I1E1 or I2E2, indicating that they were of human rotavirus origin. RNA-RNA hybridization using 21 culture-adapted strains showed that Malawian rotaviruses had a genomic RNA constellation common to either the Wa-like or DS-1 like human rotaviruses. Overall, the Malawi strains appear similar in their genetic make-up to rotaviruses described in countries where vaccine efficacy is greater, suggesting that the lower efficacy in Malawi is unlikely to be explained by the diversity of circulating strains.
doi:10.1016/j.vaccine.2011.09.119
PMCID: PMC3982048  PMID: 22520123
Rotavirus; vaccine; genotype; strain diversity; genogroup
4.  Potential Barriers to Healthcare in Malawi for Under-five Children with Cough and Fever: A National Household Survey 
Failure to access healthcare is an important contributor to child mortality in many developing countries. In a national household survey in Malawi, we explored demographic and socioeconomic barriers to healthcare for childhood illnesses and assessed the direct and indirect costs of seeking care. Using a cluster-sample design, we selected 2,697 households and interviewed 1,669 caretakers. The main reason for households not being surveyed was the absence of a primary caretaker in the household. Among 2,077 children aged less than five years, 504 episodes of cough and fever during the previous two weeks were reported. A trained healthcare provider was visited for 48.0% of illness episodes. A multivariate regression model showed that children from the poorest households (p=0.02) and children aged >12 months (p=0.02) were less likely to seek care when ill compared to those living in wealthier households and children of higher age-group respectively. Families from rural households spent more time travelling compared to urban households (68.9 vs 14.1 minutes; p<0.001). In addition, visiting a trained healthcare provider was associated with longer travel time (p<0.001) and higher direct costs (p<0.001) compared to visiting an untrained provider. Thus, several barriers to accessing healthcare in Malawi for childhood illnesses exist. Continued efforts to reduce these barriers are needed to narrow the gap in the health and healthcare equity in Malawi.
PMCID: PMC4089074  PMID: 24847595
Healthcare surveys; Health expenditure; Health services accessibility; Malaria; Pneumonia; Malawi
5.  Identification of Immunological Biomarkers Which May Differentiate Latent Tuberculosis from Exposure to Environmental Nontuberculous Mycobacteria in Children 
A positive gamma interferon (IFN-γ) response to Mycobacterium tuberculosis early secretory antigenic target-6 (ESAT-6)/culture filtrate protein-10 (CFP-10) has been taken to indicate latent tuberculosis (TB) infection, but it may also be due to exposure to environmental nontuberculous mycobacteria in which ESAT-6 homologues are present. We assessed the immune responses to M. tuberculosis ESAT-6 and cross-reactive responses to ESAT-6 homologues of Mycobacterium avium and Mycobacterium kansasii. Archived culture supernatant samples from children at 3 years post-BCG vaccination were tested for cytokine/chemokine responses to M. tuberculosis antigens. Furthermore, the IFN-γ responses to M. tuberculosis antigens were followed up for 40 children at 8 years post-BCG vaccination, and 15 TB patients were recruited as a control group for the M. tuberculosis ESAT-6 response in Malawi. IFN-γ enzyme-linked immunosorbent assays (ELISAs) on supernatants from diluted whole-blood assays, IFN-γ enzyme-linked immunosorbent spot (ELISpot) assays, QuantiFERON TB Gold-In Tube tests, and multiplex bead assays were performed. More than 45% of the responders to M. tuberculosis ESAT-6 showed IFN-γ responses to M. avium and M. kansasii ESAT-6. In response to M. tuberculosis ESAT-6/CFP-10, interleukin 5 (IL-5), IL-9, IL-13, and IL-17 differentiated the stronger IFN-γ responders to M. tuberculosis ESAT-6 from those who preferentially responded to M. kansasii and M. avium ESAT-6. A cytokine/chemokine signature of IL-5, IL-9, IL-13, and IL-17 was identified as a putative immunological biosignature to differentiate latent TB infection from exposure to M. avium and M. kansasii in Malawian children, indicating that this signature might be particularly informative in areas where both TB and exposure to environmental nontuberculous mycobacteria are endemic.
doi:10.1128/CVI.00620-13
PMCID: PMC3910933  PMID: 24285818
6.  G8 rotaviruses with conserved genotype constellations detected in Malawi over 10 years (1997–2007) display frequent gene reassortment among strains co-circulating in humans 
The Journal of General Virology  2013;94(Pt 6):1273-1295.
Rotavirus A, the most common cause of severe diarrhoea in children worldwide, occurs in five major VP7 (G) and VP4 (P) genotype combinations, comprising G1P[8], G2P[4], G3P[8], G4P[8] and G9P[8]. However, G8, a common bovine rotavirus genotype, has been reported frequently among children in African countries. Surveillance of rotavirus gastroenteritis conducted in a sentinel hospital in Blantyre, Malawi between 1997 and 2007 provided a rare opportunity to examine the whole genotype constellation of G8 strains and their evolution over time. A sample of 27 (9.0 %) of 299 G8 strains was selected to represent each surveillance year and a range of P genotypes, which shifted in predominance from P[6] to P[4] and P[8] during the study period. Following cell culture adaptation, whole genome sequencing demonstrated that the genetic background of 26 strains possessed the DS-1 genotype constellation. A single G8P[6] strain was a reassortant in which both NSP2 and NSP5 genes from strains with the Wa genotype constellation had been inserted into a strain with the DS-1 genotype background. Phylogenetic analysis suggested frequent reassortment among co-circulating strains with the DS-1 genotype constellation. Little evidence was identified to suggest the introduction of contemporary bovine rotavirus genes into any of the 27 G8 strains examined. In conclusion, Malawian G8 strains are closely related to other human strains with the DS-1 genotype constellation. They have evolved over the last decade through genetic reassortment with other human rotaviruses, changing their VP4 genotypes while maintaining a conserved genotype constellation for the remaining structural and non-structural proteins.
doi:10.1099/vir.0.050625-0
PMCID: PMC3945219  PMID: 23407423
7.  Campylobacter Infection in Children in Malawi Is Common and Is Frequently Associated with Enteric Virus Co-Infections 
PLoS ONE  2013;8(3):e59663.
Background
Campylobacter species are the most common cause of bacterial gastroenteritis in the developed world. However, comparatively few studies have determined the epidemiological features of campylobacteriosis in resource-poor settings.
Methods
A total of 1,941 faecal specimens collected from symptomatic (diarrhoeic) children and 507 specimens from asymptomatic (non-diarrhoeic) children hospitalised in Blantyre, Malawi, between 1997 and 2007, and previously tested for the presence of rotavirus and norovirus, was analysed for C. jejuni and C. coli using a real time PCR assay.
Results
Campylobacter species were detected in 415/1,941 (21%) of diarrhoeic children, with C. jejuni accounting for 85% of all cases. The median age of children with Campylobacter infection was 11 months (range 0.1–55 months), and was significantly higher than that for children with rotavirus and norovirus (6 months and 7 months respectively; P<0.001). Co-infection with either rotavirus or norovirus was noted in 41% of all cases in the diarrhoeic group. In contrast, the detection rate of Campylobacter in the non-diarrhoeic group was 14%, with viral co-infection identified in 16% of children with Campylobacter. There was no association between Campylobacter detection rate and season over the 10 year period.
Discussion
Using molecular detection methodology in hospitalised Malawian children, we have demonstrated a high prevalence of Campylobacter infection, with frequent viral co-infection. The burden of Campylobacter infection in young African children may be greater than previously recognised.
doi:10.1371/journal.pone.0059663
PMCID: PMC3608717  PMID: 23555739
8.  Analysis of Schistosomiasis haematobium Infection Prevalence and Intensity in Chikhwawa, Malawi: An Application of a Two Part Model 
Background
Urinary Schistosomiasis infection, a common cause of morbidity especially among children in less developed countries, is measured by the number of eggs per urine. Typically a large proportion of individuals are non-egg excretors, leading to a large number of zeros. Control strategies require better understanding of its epidemiology, hence appropriate methods to model infection prevalence and intensity are crucial, particularly if such methods add value to targeted implementation of interventions.
Methods
We consider data that were collected in a cluster randomized study in 2004 in Chikhwawa district, Malawi, where eighteen (18) villages were selected and randomised to intervention and control arms. We developed a two-part model, with one part for analysis of infection prevalence and the other to model infection intensity. In both parts of the model we adjusted for age, sex, education level, treatment arm, occupation, and poly-parasitism. We also assessed for spatial correlation in the model residual using variogram analysis and mapped the spatial variation in risk. The model was fitted using maximum likelihood estimation.
Results and discussion
The study had a total of 1642 participants with mean age of 32.4 (Standard deviation: 22.8), of which 55.4 % were female. Schistosomiasis prevalence was 14.2 %, with a large proportion of individuals (85.8 %) being non-egg excretors, hence zero-inflated data. Our findings showed that S. haematobium was highly localized even after adjusting for risk factors. Prevalence of infection was low in males as compared to females across all the age ranges. S. haematobium infection increased with presence of co-infection with other parasite infection. Infection intensity was highly associated with age; with highest intensity in school-aged children (6 to 15 years). Fishing and working in gardens along the Shire River were potential risk factors for S. haematobium infection intensity. Intervention reduced both infection intensity and prevalence in the intervention arm as compared to control arm. Farmers had high infection intensity as compared to non farmers, despite the fact that being a farmer did not show any significant association with probability of infection.
These results evidently indicate that infection prevalence and intensity are associated with risk factors differently, suggesting a non-singular epidemiological setting. The dominance of agricultural, socio-economic and demographic factors in determining S. haematobium infection and intensity suggest that disease transmission and control strategies should continue centring on improving socio-economic status, environmental modifications to control S. haematobium intermediate host snails and mass drug administration, which may be more promising approaches to disease control in high intensity and prevalence settings.
Author Summary
Schistosomiasis is one of the great causes of morbidity among school aged children in the tropical region and Sub Saharan Africa in particular. It's mainly transmitted through contact with water infested with intermediate host snail Cercariae. Currently, over 200 million people are estimated to be infected in SSA alone. Here, we used robust and contemporary statistical methods in a two part application to analyse risk factors for S. haematobium infection intensity and prevalence. We found that S. haematobium was more common in younger children as compared to older children, thus making the infection and prevalence age dependent. We also found that mass chemotherapy reduced both infection prevalence and intensity. We found that dominance of agricultural, socio-economic and demographic factors in determining S. haematobium infection risk in the villages carries important implications for disease surveillance and control strategies. Therefore disease transmission and control strategies centered on improving strategies involving socio-economic status, environmental modifications to control S. haematobium intermediate host snails and mass drug administration may be more promising approaches to disease control in high intensity and prevalence settings.
doi:10.1371/journal.pntd.0002131
PMCID: PMC3605235  PMID: 23556017
9.  Characterizing the emergence and persistence of drug resistant mutations in HIV-1 subtype C infections using 454 ultra deep pyrosequencing 
Background
The role of HIV-1 RNA in the emergence of resistance to antiretroviral therapies (ARTs) is well documented while less is known about the role of historical viruses stored in the proviral DNA. The primary focus of this work was to characterize the genetic diversity and evolution of HIV drug resistant variants in an individual’s provirus during antiretroviral therapy using next generation sequencing.
Methods
Blood samples were collected prior to antiretroviral therapy exposure and during the course of treatment from five patients in whom drug resistance mutations had previously been identified using consensus sequencing. The spectrum of viral variants present in the provirus at each sampling time-point were characterized using 454 pyrosequencing from multiple combined PCR products. The prevalence of viral variants containing drug resistant mutations (DRMs) was characterized at each time-point.
Results
Low abundance drug resistant viruses were identified in 14 of 15 sampling time-points from the five patients. In all individuals DRMs against current therapy were identified at one or more of the sampling time-points. In two of the five individuals studied these DRMs were present prior to treatment exposure and were present at high prevalence within the amplified and sequenced viral population. DRMs to drugs other than those being currently used were identified in four of the five individuals.
Conclusion
The presence of DRMs in the provirus, regardless of their observed prevalence did not appear to have an effect on clinical outcomes in the short term suggesting that the drug resistant viral variants present in the proviral DNA do not appear to play a role in the short term in facilitating the emergence of drug resistance.
doi:10.1186/1471-2334-13-52
PMCID: PMC3740783  PMID: 23363532
HIV-1; Drug resistance; Subtype C; Malawi; Ultradeep sequencing; Proviral DNA
10.  Human rotavirus vaccine Rotarix™ provides protection against diverse circulating rotavirus strains in African infants: a randomized controlled trial 
BMC Infectious Diseases  2012;12:213.
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
doi:10.1186/1471-2334-12-213
PMCID: PMC3462149  PMID: 22974466
11.  High accuracy of home-based community rapid HIV testing in rural Malawi 
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.
doi:10.1097/QAI.0b013e3181f98628
PMCID: PMC3248920  PMID: 21934554
HIV serodiagnosis; quality control; home care; population surveillance; Malawi
12.  Combining Qualitative and Quantitative Evidence to Determine Factors Leading to Late Presentation for Antiretroviral Therapy in Malawi 
PLoS ONE  2011;6(11):e27917.
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.
doi:10.1371/journal.pone.0027917
PMCID: PMC3218069  PMID: 22114727
13.  Reverse transcriptase drug resistance mutations in HIV-1 subtype C infected patients on ART in Karonga District, Malawi 
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
doi:10.1186/1742-6405-8-38
PMCID: PMC3215651  PMID: 21995490
HIV-1; drug resistance; subtype C; ART; Malawi; Reverse transcriptase
14.  The Burden of Selected Chronic Non-Communicable Diseases and Their Risk Factors in Malawi: Nationwide STEPS Survey 
PLoS ONE  2011;6(5):e20316.
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.
doi:10.1371/journal.pone.0020316
PMCID: PMC3100352  PMID: 21629735
15.  Drug Resistance Mutations in Drug-Naive HIV Type 1 Subtype C-Infected Individuals from Rural 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.
doi:10.1089/aid.2010.0203
PMCID: PMC3068870  PMID: 20950147
16.  Population-Level Reduction in Adult Mortality after Extension of Free Anti-Retroviral Therapy Provision into Rural Areas in Northern Malawi 
PLoS ONE  2010;5(10):e13499.
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.
doi:10.1371/journal.pone.0013499
PMCID: PMC2957442  PMID: 20976068
17.  HIV and the risk of tuberculosis due to recent transmission over 12 years in Karonga District, Malawi☆ 
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.
doi:10.1016/j.trstmh.2009.03.013
PMCID: PMC2784949  PMID: 19362727
HIV; Tuberculosis; Mycobacterium tuberculosis; Molecular epidemiology; Transmission; Malawi
18.  Serotype G12 Rotaviruses, Lilongwe, Malawi 
Emerging Infectious Diseases  2009;15(1):87-90.
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.
doi:10.3201/eid1501.080427
PMCID: PMC2660691  PMID: 19116060
Gastroenteritis; rotavirus; electropherotype; VP7; VP4; Malawi; dispatch
19.  Determinants of Cluster Size in Large, Population-Based Molecular Epidemiology Study of Tuberculosis, Northern Malawi 
Emerging Infectious Diseases  2008;14(7):1060-1066.
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.
doi:10.3201/eid1407.060468
PMCID: PMC2600342  PMID: 18598626
Tuberculosis; HIV; RFLP; tuberculosis transmission; Africa; research
20.  The geographical distribution of lymphatic filariasis infection in Malawi 
Filaria Journal  2007;6:12.
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.
doi:10.1186/1475-2883-6-12
PMCID: PMC2233609  PMID: 18047646
21.  Point-of-Use Water Treatment and Use among Mothers in Malawi 
Emerging Infectious Diseases  2007;13(7):1077-1080.
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.
doi:10.3201/eid1307.070767
PMCID: PMC2878214  PMID: 18214185
Malawi; diarrhea; social marketing; dispatch
22.  Mycobacterium tuberculosis Beijing Genotype, Northern Malawi 
Emerging Infectious Diseases  2005;11(1):150-153.
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.
doi:10.3201/eid1101.040869
PMCID: PMC3294335  PMID: 15705343
tuberculosis; RFLP; Africa; drug resistance; dispatch
23.  Mycobacterial Purified Protein Derivatives Stimulate Innate Immunity: Malawians Show Enhanced Tumor Necrosis Factor Alpha, Interleukin-1β (IL-1β), and IL-10 Responses Compared to Those of Adolescents in the United Kingdom  
Infection and Immunity  2004;72(3):1807-1811.
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.
doi:10.1128/IAI.72.3.1807-1811.2004
PMCID: PMC356017  PMID: 14977992
24.  Adult mortality and probable cause of death in rural northern Malawi in the era of HIV treatment 
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.
doi:10.1111/j.1365-3156.2012.02929.x
PMCID: PMC3443368  PMID: 22943382
HIV; cause of death; Africa; verbal autopsy

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