The Tingathe Surge: a multi-strategy approach to accelerate HIV case finding in Malawi.

SETTING: Nineteen health facilities in rural, southeastern Malawi. OBJECTIVE: To describe the implementation and results of a 6-week intervention to accelerate human immunodeficiency virus (HIV) case finding. DESIGN: Six HIV testing strategies were simultaneously implemented. Routinely collected data from Ministry of Health registers were used to determine the number of HIV tests performed and of new cases identified. The weekly averages of the total number of tests and new cases before and during the intervention were compared. Testing by age group and sex was described. The percentage yield of new cases was compared by testing strategy. RESULTS: Of 29 703 HIV tests conducted, 1106 (3.7%) were positive. Of the total number of persons tested, 69.5% were women and 75.5% were aged >15 years. The yield of positive test results was 3.5% among women, 4.3% among men, 4.4% among those aged >15 years and 1.5% among those aged ⩽15 years. The average weekly number of tests increased 106.7% from 3337 to 6896 (P = 0.002). The average weekly number of positive cases identified increased 51.9% from 158 to 240 (P = 0.017). The testing strategy with the highest yield resulted in a 6.0% yield; the lowest was 1.3%. The yield for all strategies, except one, was highest in adult men. CONCLUSION: A multi-strategy approach to HIV testing and counseling can be an effective means of accelerating HIV case finding.

Burden of disease and risk factors for death among children treated for tuberculosis in Malawi.

SETTING: Tuberculosis (TB) is a leading cause of childhood death. Patient-level data on pediatric TB in Malawi that can be used to guide programmatic interventions are limited. OBJECTIVE: To describe pediatric TB case burden, disease patterns, treatment outcomes, and risk factors for death and poor outcome. DESIGN: We conducted a retrospective cohort study utilizing routine data. Odds ratios (ORs) for factors associated with poor outcome and death were calculated using generalized estimating equations. RESULTS: Children represented 8% (371/4642) of TB diagnoses. The median age was 7 years (interquartile range 2.8-11); 32.8% (113/345) were human immunodeficiency virus (HIV) infected. Of these, 54.0% were on antiretroviral therapy (ART) at the time of anti-tuberculosis treatment (ATT) initiation, 21.2% started ART during ATT, and 24.8% had no documented ART. The treatment success rate was 77.3% (11.2% cured, 66.1% completed treatment), with 22.7% experiencing poor outcomes (9.5% died, 13.2% were lost to follow-up). Being on ART at the time of ATT initiation was associated with increased odds of death compared to beginning ART during treatment (adjusted OR 2.75, 95%CI 1.27-5.96). CONCLUSION: Children represent a small proportion of diagnosed TB cases and experience poor outcomes. Higher odds of death among children already on ART raises concerns over the management of these children. Further discussion of and research into pediatric-specific strategies is required to improve case finding and outcomes.

The quality and diagnostic value of open narratives in verbal autopsy: a mixed-methods analysis of partnered interviews from Malawi.

BACKGROUND: Verbal autopsy (VA), the process of interviewing a deceased's family or caregiver about signs and symptoms leading up to death, employs tools that ask a series of closed questions and can include an open narrative where respondents give an unprompted account of events preceding death. The extent to which an individual interviewer, who generally does not interpret the data, affects the quality of this data, and therefore the assigned cause of death, is poorly documented. We aimed to examine inter-interviewer reliability of open narrative and closed question data gathered during VA interviews. METHODS: During the introduction of VA data collection, as part of a larger study in Mchinji district, Malawi, we conducted partner interviews whereby two interviewers independently recorded open narrative and closed questions during the same interview. Closed questions were collected using a smartphone application (mobile-InterVA) and open narratives using pen and paper. We used mixed methods of analysis to evaluate the differences between recorded responses to open narratives and closed questions, causes of death assigned, and additional information gathered by open narrative. RESULTS: Eighteen partner interviews were conducted, with complete data for 11 pairs. Comparing closed questions between interviewers, the median number of differences was 1 (IQR: 0.5-3.5) of an average 65 answered; mean inter-interviewer concordance was 92% (IQR: 92-99%). Discrepancies in open narratives were summarized in five categories: demographics, history and care-seeking, diagnoses and symptoms, treatment and cultural. Most discrepancies were seen in the reporting of diagnoses and symptoms (e.g., malaria diagnosis); only one pair demonstrated no clear differences. The average number of clinical symptoms reported was 9 in open narratives and 20 in the closed questions. Open narratives contained additional information on health seeking and social issues surrounding deaths, which closed questions did not gather. CONCLUSIONS: The information gleaned during open narratives was subject to inter-interviewer variability and contained a limited number of symptom indicators, suggesting that their use for assigning cause of death is questionable. However, they contained rich information on care-seeking, healthcare provision and social factors in the lead-up to death, which may be a valuable source of information for promoting accountable health services.

Risk factors for mortality in Malawian children with human immunodeficiency virus and tuberculosis co-infection.

SETTING: A large urban pediatric human immunodeficiency virus (HIV) clinic in Lilongwe, Malawi. OBJECTIVE: To identify demographic and clinical risk factors for mortality in children co-infected with HIV and tuberculosis (TB). DESIGN: A retrospective cohort study of HIV-infected children (aged <18 years) enrolled between October 2004 and October 2010 with at least one current or historical TB diagnosis. Descriptive statistics and logistic regression analyses were performed to determine factors associated with mortality. RESULTS: A total of 1561 patients met the inclusion criteria, representing 32% of patients ever enrolled. Median age at TB diagnosis was 3.8 years (interquartile range 1.5-7.4); 60.9% had severe immune suppression and 47.6% of those with available data had some degree of acute malnutrition at TB diagnosis. Of the 1113 patients with known outcomes, 225 (20.2%) died. Children with TB-HIV co-infection not initiated on antiretroviral therapy (ART) at any time were 8.8 times more likely to die compared to those initiated on ART 0-2 months after initiation of anti-tuberculosis treatment (adjusted OR 8.83, 95%CI 4.42-17.63). Severe immunosuppression and World Health Organization Stage IV were also associated with mortality. CONCLUSIONS: Pediatric TB-HIV co-infection is common and mortality is high in this cohort of Malawian children. Prompt initiation of ART should be emphasized in this high-risk patient population.

Sexually Transmitted Infection (STI) screening, case and contact treatment, and condom promotion resulting in STI reduction two years later in rural Malawi.

As part of a longitudinal cohort study in rural Malawi in 2000, 469 men and 758 women were asked to respond to a series of surveys, were tested for gonorrhea and chlamydia, and received their results and treatment, if applicable, for themselves and up to 2 partners if positive for either sexually transmitted infection (STI). Two years later, in 2002, 328 men and 525 women were again asked to respond to survey questions, tested again for gonorrhea and chlamydia, and were also tested for HIV--of these, 247 men and 453 women had also given urine samples in 2000. In 2000, the gonorrhea and chlamydia prevalence was 6.2% and 5.8% among men, and 3.6% and 4.9% among women. Two years later, prevalence of gonorrhea and chlamydia was 0.7% and 1.4% among men, and 1.3% and 1.1% among women. Although we did not test for HIV in the first round, the HIV prevalence in 2002 was 19.2%. The implications of the findings are discussed in the context of interventions for STI prevention and to reduce HIV transmission in sub-Saharan Africa.

Strategies developed and implemented by women's groups to improve mother and infant health and reduce mortality in rural Malawi.

We evaluated the strategies to tackle maternal and infant health problems developed by women's groups in rural Malawi. Quantitative data were analyzed on strategies developed by 184 groups at two of the meetings in the community action cycle (attended by 3365 and 3047 women). Data on strategies implemented was collected through a survey of the 197 groups active in January 2010. Qualitative data on the identification and implementation of strategies was collected through 17 focus group discussions and 12 interviews with men and women. To address the maternal and child health problems identified the five most common strategies identified were: health education sessions, bicycle ambulances, training of traditional birth attendants, wetland vegetable garden (dimba garden) cultivation and distribution of insecticide treated bednets (ITNs). The five most common strategies actually implemented were: dimba garden cultivation, health education sessions, ITN distribution, health programme radio listening clubs and clearing house surroundings. The rationale behind the strategies and the factors facilitating and hindering implementation are presented. The potential impact of the strategies on health is discussed. Women's groups help communities to take control of their health issues and have the potential to reduce neonatal, infant and maternal mortality and morbidity in the longer term.

Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants.

Identifying the specific genetic characteristics of successfully transmitted variants may prove central to the development of effective vaccine and microbicide interventions. Although human immunodeficiency virus transmission is associated with a population bottleneck, the extent to which different factors influence the diversity of transmitted viruses is unclear. We estimate here the number of transmitted variants in 69 heterosexual men and women with primary subtype C infections. From 1,505 env sequences obtained using a single genome amplification approach we show that 78% of infections involved single variant transmission and 22% involved multiple variant transmissions (median of 3). We found evidence for mutations selected for cytotoxic-T-lymphocyte or antibody escape and a high prevalence of recombination in individuals infected with multiple variants representing another potential escape pathway in these individuals. In a combined analysis of 171 subtype B and C transmission events, we found that infection with more than one variant does not follow a Poisson distribution, indicating that transmission of individual virions cannot be seen as independent events, each occurring with low probability. While most transmissions resulted from a single infectious unit, multiple variant transmissions represent a significant fraction of transmission events, suggesting that there may be important mechanistic differences between these groups that are not yet understood.

Community-based distribution of sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria during pregnancy improved coverage but reduced antenatal attendance in southern Malawi.

OBJECTIVE: To evaluate the impact of a 2-year programme for community-based delivery of sulfadoxine-pyrimethamine (SP) on intermittent preventive treatment during pregnancy coverage, antenatal clinic attendance and pregnancy outcome. METHODS: Fourteen intervention and 12 control villages in the catchment areas of Chikwawa and Ngabu Government Hospitals, southern Malawi, were selected. Village-based community health workers were trained in information, education and counselling on malaria control in pregnancy and the importance of attending antenatal clinics and promoted these messages to pregnant women. In the intervention group community health workers also distributed SP to pregnant women. RESULTS: In the control area, coverage of intermittent preventive treatment during pregnancy (>2 doses) was low before (44.1%) and during the intervention (46.1%). In the intervention area, coverage increased from 41.5% to 82.9% (P < 0.01). Antenatal clinic attendance (>2 visits) was maintained in control villages at above 90%, but fell in intervention villages from 87.3% to 51.5% (P < 0.01). Post-natal malaria parasitaemia prevalence fell in women from both study areas during the intervention phase (P < 0.05). Increasing the coverage of intermittent preventive treatment during pregnancy to >40% did not significantly improve maternal haemoglobin or reduce low birthweight prevalence. CONCLUSIONS: Better coverage of community-based intermittent preventive treatment during pregnancy can lower attendance at antenatal clinics; thus its effect on pregnancy outcome and antenatal attendance need to be monitored.

Women's groups' perceptions of neonatal and infant health problems in rural Malawi.

AIMS: To present the perceptions of women in rural Malawi regarding the health problems affecting neonates and infants and to explore the relevance of these perceptions for child health policy and strategy in Malawi. METHODS: Women's groups in Mchinji district identified newborn and infant health problems (204 groups, 3484 women), prioritised problems they considered most important (204 groups, 3338 women) and recorded these problems on monitoring forms. Qualitative data was obtained through 6 focus-group discussions with the women's groups and 22 interviews with individuals living in women's group communities but not attending groups. RESULTS: Women in Malawi do not define the neonatal period according to any epidemiological definition. In order of importance they identified and prioritised the following problems for newborns and infants: diarrhoea, infection, preterm birth, tetanus, malaria, asphyxia, respiratory tract infection, hypothermia, jaundice, convulsions and malnutrition. CONCLUSION: This study suggests that women in rural Malawi collectively have a developed understanding of neonatal and infant health problems. This makes a strong argument for the involvement of lay people in policy and strategy development and also suggests that this capacity, harnessed and strengthened through community mobilisation approaches, has the potential to improve neonatal and infant health and reduce mortality.

Estimation of effectiveness of interventions for malaria control in pregnancy using the screening method.

BACKGROUND: The evaluation of the effectiveness of antimalarial drugs and bed net use in pregnant women is an important aspect of monitoring and surveillance of malaria control in pregnancy. In principle the screening method for assessing vaccine efficacy can be applied in non-vaccine settings for assessing interventions for malaria control in pregnancy. METHODS: In this analysis field data on the proportion of placental malaria cases treated with two doses of sulphadoxine-pyrimethamine (SP) and the uptake of two doses of SP in the antenatal clinic was used in a case-coverage method to assess the protective effectiveness (PE) of intermittent preventive treatment with SP for malaria control in pregnancy. PE was assessed using placental malaria, low birthweight and maternal anaemia at delivery as outcome variables. The method was also applied to an evaluation of the protective effectiveness of self-reported use of impregnated bed nets (ITNs). RESULTS: Effectiveness was highest for reduction of low birthweight in multigravidae (87.2%, 95% CI, 83.2-91.3%). PE was lower for placental malaria (61.6% primigravidae, 28.5% multigravidae), and maternal anaemia (Hb < 8.0 g/dl, 37.8% primigravidae, 29.6% multigravidae). Estimates for PE of self-reported use of ITNs gave values for all three outcome parameters that were much lower than for SP use. For women of all parties effectiveness estimates for reduction of low birthweight were 22% (95% CI, 17.7-26.4), prevention of placental malaria (all types) 7.1% (95% CI, 4.4-9.8), prevention of active placental infection 38.9% (95% CI, 27.4-50.4), and for maternal anaemia 8.8% (95% CI, 0-20.0). CONCLUSIONS: The case-coverage method could provide a useful and practical approach to routine monitoring and evaluation of drug interventions to control malaria in pregnancy and has potentially wide applications. Effectiveness estimates related to reported ITN use in pregnancy may be less reliable. The method should be further evaluated using currently available data sets.

In-vivo parasitological response to sulfadoxine-pyrimethamine in pregnant women in southern Malawi.

BACKGROUND: Malaria in pregnancy is a significant cause of maternal and infant morbidity and mortality. Malawi adopted intermittent preventive treatment with sulfadoxinepyrimethamine (SP) for the control of malaria in pregnancy in 1993. However there is little information on the in-vivo SP efficacy in pregnant women. This study was conducted to determine: prevalence of malaria and anaemia at the first antenatal visit and rate of parasitological failure to SP in pregnancy. METHODS: A cross-sectional followed by a prospective cohort study was conducted in women attending antenatal care clinic at Montfort Hospital in Lower Shire Valley from June 2004 to February 2005. Women were screened for malaria and anaemia at the first antenatal visit. After taking SP under direct observation, women with malaria parasitaemia were followed up to day 14 to determine parasitological response. RESULTS: Of 961 women screened, 9% had malaria, 77% had anaemia (HB<11.0g/dl), 24% had moderate anaemia (HB 7.0-8.9g/dl) and 6% had severe anaemia (HB<7.0g/dl). Malaria was significantly more frequent in primigravidae, the second trimester and in the post- rainy season (all p <0.05). Moderate anaemia (Hb < 9.0g/dl) was significantly more common in adolescents and primigravidae (both p <0.05). In the14-day follow up study, loss to follow up was 13%. Of the 74 women who completed the follow up, 89% cleared malaria parasites successfully and 11% had parasitological failure. Parasitological failures were all of the R1 type except for one with R2 failure. CONCLUSION: Anaemia prevalence was high at first antenatal visit in this population. Rate of parasitological failure to SP in pregnancy increased from 5% in 1996 to 11% in 2004.

In-Vivo Parasitological Response to sulfadoxine-pyrimethamine in Pregnant Women in Southern Malawi

Background : Malaria in pregnancy is a significant cause of maternal and infant morbidity and mortality. Malawi adopted intermittent preventive treatment with sulfadoxinepyrimethamine (SP) for the control of malaria in pregnancy in 1993. However there is little information on the in-vivo SP efficacy in pregnant women. This study was conducted to determine: prevalence of malaria and anaemia at the first antenatal visit and rate of parasitological failure to SP in pregnancy. Methods: A cross-sectional followed by a prospective cohort study was conducted in women attending antenatal care clinic at Montfort Hospital in Lower Shire Valley from June 2004 to February 2005. Women were screened for malaria and anaemia at the first antenatal visit. After taking SP under direct observation; women with malaria parasitaemia were followed up to day 14 to determine parasitological response.Results: Of 961 women screened; 9 had malaria; 77 had anaemia (HB11.0g/dl); 24 had moderate anaemia (HB 7.0-8.9g/dl) and 6 had severe anaemia (HB7.0g/dl). Malaria was significantly more frequent in primigravidae; the second trimester and in the post- rainy season (all p 0.05). Moderate anaemia (Hb 9.0g/dl) was significantly more common in adolescents and primigravidae (both p 0.05). In the14-day follow up study; loss to follow up was 13. Of the 74 women who completed the follow up; 89 cleared malaria parasites successfully and 11 had parasitological failure. Parasitological failures were all of the R1 type except for one with R2 failure

Genotypic analysis of the protease and reverse transcriptase of HIV type 1 subtype C isolates from antiretroviral drug-naive adults in Malawi.

The protease (PR) and reverse transcriptase (RT) regions of HIV-1 isolates from 21 antiretroviral (ARV)-naive Malawian adults were sequenced and analyzed to determine the prevalence of drug resistance-associated mutations in this population. Phylogenetic analysis confirmed that all isolates grouped with HIV-1 subtype C, the predominant subtype in Malawi. No major mutations associated with resistance to PR inhibitors (PIs), nucleoside RT inhibitors (NRTIs), or nonnucleoside RT inhibitors (NNRTIs) were found. In contrast, accessory mutations were found in the protease region at positions 10, 20, 36, 63, 77, and 93, and in the RT region at positions 118, 211, and 214. Further studies will be needed to determine the clinical impact of these polymorphisms on viral susceptibility to existing antiretroviral drugs.

Neonatal sepsis: an international perspective.

Neonatal infections currently cause about 1.6 million deaths annually in developing countries. Sepsis and meningitis are responsible for most of these deaths. Resistance to commonly used antibiotics is emerging and constitutes an important problem world wide. To reduce global neonatal mortality, strategies of proven efficacy, such as hand washing, barrier nursing, restriction of antibiotic use, and rationalisation of admission to neonatal units, need to be implemented. Different approaches require further research.

Childhood tuberculosis in Malawi: caseload, diagnostic practices and treatment outcomes.

There were 22,982 cases of TB registered in Malawi in 1998, of which 2739 (11.9%) were children. Children accounted for 11.3% of all case notifications with smear-positive pulmonary TB (PTB), 21.3% with smear-negative PTB and 15.9% with extrapulmonary TB (EPTB). A significantly higher proportion of TB cases were diagnosed in central hospitals. Only 45% of children completed treatment. There were high rates of death (17%), default (13%) and unknown treatment outcomes (21%). Treatment outcomes were worse in younger children and in children with smear-negative PTB. In 2001, all 44 non-private hospitals in Malawi that register and treat children with tuberculosis (TB) were surveyed to determine actual diagnostic practice. This cross sectional study identified 150 children aged 14 years or below in hospital receiving anti-TB treatment, 98 with pulmonary TB (PTB) and 52 with extrapulmonary TB (EPTB). Median duration of illness was 8 weeks. Most patients had fever, no response to anti-malarial treatment and antibiotics, and 40% had a positive family history of TB. Nearly 45% had weight for age < 60%. Diagnosis was mainly based on clinical features and radiography, with less than 10% having tuberculin skin tests or HIV serology, and very few having other sophisticated investigations. Diagnostic difficulties make it difficult to accurately define the actual burden of childhood TB in Malawi. Diagnostic practices are poor and treatment outcomes unsatisfactory.

Detection of bloodstream pathogens in a bacille Calmette-Guérin (BCG)-vaccinated pediatric population in Malawi: a pilot study.

Children in Malawi receive bacille Calmette-Guérin (BCG) vaccination within the first 3 days of life. Thus, we hypothesized that Malawian children infected with the human immunodeficiency type 1 virus (HIV-1) might be particularly vulnerable to dissemination of the BCG Mycobacterium bovis strain with which they were vaccinated. Following informed consent by parents, we studied children admitted to a Malawi general hospital during the 1998 wet and dry seasons. Blood from cohorts of acutely ill children was cultured for bacteria, including mycobacteria, and fungi, and tested for anti-HIV-1 antibodies. It was shown that non-typhi Salmonella and Escherichia coli were the predominant bloodstream pathogens during the wet and dry seasons, and that bloodstream dissemination of the BCG M. bovis strain is uncommon in HIV-1-infected children who receive the BCG vaccine.

Long term survival of children with Burkitt lymphoma in Malawi after cyclophosphamide monotherapy.

BACKGROUND: Between 1991 and 1997, limited funding at times restricted available treatment for children with Burkitt lymphoma (BL) to cyclophosphamide (CPM) monotherapy at Lilongwe Central Hospital, Malawi. Our objective was to assess long-term survival in Malawian children with Burkitt lymphoma (BL) who had received one or more treatments with intravenous CPM at 40 mg/kg/dose at 14-day intervals. PROCEDURE AND RESULTS: The study population consisted of 92 children in whom BL had been confirmed on fine needle aspirates (FNA), a home address had been documented on discharge from hospital, and the treatment records could be verified. Only the clinical site(s) of disease had been recorded. The M:F ratio was 1.4 and median age 8 years. A clinical officer on motorcycle attempted to locate the given addresses and interview parents or other sources. In 19 patients, the address was incorrect. Of 73 evaluable patients, 40 children are alive at a mean follow-up time of 59 (range: 29-104) months. The survival rate was 63.5% in 52 children with BL of the head only, and 33.3% in 21 children with primary disease involving the abdomen or other sites. Survivors had received a median number of 6 (range: 1-12), non-survivors 4 (range: 1-12), and untracable children 3 (range: 1-11) courses of CPM. CONCLUSIONS: We confirmed that CPM could cure children with facial and abdominal BL. The unavoidable bias in the selection of patients and the variable amount of CPM given, precludes accurate survival estimates. A prospective study with proper staging, assessment of FNA, marrow and cerebrospinal fluid with modern techniques, a standard treatment protocol, and adequate follow-up will better define the current therapeutic value of CPM monotherapy. CPM can be purchased at about 3 US dollars per 500 mg.

Childhood tuberculosis in Malawi: nationwide case-finding and treatment outcomes.

SETTING: All 43 non-private hospitals (three central, 22 [corrected] district and 18 [corrected] mission) in Malawi that register and treat adult and paediatric TB cases. OBJECTIVE: To assess the rate, pattern and treatment outcome of childhood TB case notifications in Malawi in 1998. DESIGN: Retrospective data collection using TB registers, treatment cards and information from health centre registers. Information was collected on number of cases, types of TB and treatment outcomes using standardised definitions. RESULTS: There were 22,982 cases of TB registered in Malawi in 1998, of whom 2,739 (11.9%) were children. Children accounted for 1.3% of all case notifications with smear-positive pulmonary TB (PTB), 21.3% with smear-negative PTB and 15.9% with extra-pulmonary TB (EPTB). Estimated rates of TB in children were 78/ 100,000 in those aged less than one year, 83/100,000 in those aged 1-4 years and 33/100,000 in those aged 5-14 years. A significantly higher proportion of TB cases was diagnosed in central hospitals. Only 45% of children completed treatment. There were high rates of death (17%), default (13%) and unknown treatment outcomes (21%). Treatment outcomes were worse in younger children and in children with smear-negative PTB. Treatment completion was best (76%) and death rates lowest (11%) for the 127 children with smear-positive PTB. CONCLUSION: Childhood TB is common in Malawi and treatment outcomes are poor. Research should be directed towards improved diagnosis and follow-up of children with TB, and the National TB Programme should support appropriate management of childhood contacts of smear positive PTB cases.

Age-related differences in cell-specific cytokine production by acutely ill Malawian patients.

Age-related changes in human cell-specific cytokine responses to acute illness have not been well examined. We therefore evaluated age-related differences in T, B and natural killer (NK) peripheral blood lymphocyte cytokine responses of 309 acutely ill hospitalized people in Malawi, Africa, < 1 month-61 years of age. We used four-colour flow cytometry and performed Wilcoxon rank sum and Kruskal-Wallis tests, Pearson (rp) and Spearman (rs) correlations, and linear and logistic regression analyses to control for human immunodeficiency virus infection (HIV) status, the percentages of lymphocytes expressing CD4, and the nature of the acute infection. The percentages of CD8- and CD8+ T cells producing induced IL-8 decreased with age (rs = -0.44 and -0.53). The percentages of T cells producing TNF-alpha were higher, and the percentages producing IL-10 were lower, in those > or =13 than those < 13 years old (medians: 17.7 versus 10.5 and 1.4 versus 3.0, respectively). The percentages of CD8- T cells producing IFN-gamma were higher and stable in those > or =1 year old compared to infants (medians: 23.5 versus 10.4); the percentages of NK producing IFN-gamma were higher post-infancy and then declined to relatively low levels with increasing age. The percentages of T cells producing IL-2 were highest in those 5- <31 years old (median 5.6) and lowest in those > or =31 years old (median 1.9). The ratios of the percentages of T cells producing IL-4 to those producing IL-8 and to those producing IL-10 both increased with age. These data suggest that innate immunity, represented by NK IFN-gamma production, dominates in early life. A number of shifts occur after infancy and before adolescence, including a proinflammatory shift from IL-8 to TNF-gamma and a type 2 shift from IL-10 to IL-4 dominance. These findings suggest distinct age-related differences in the human response to acute illness and may be useful in directing future efforts at immunomodulatory therapies.

Changes in haemoglobin levels in infants in Malawi: effect of low birth weight and fetal anaemia.

OBJECTIVES: To examine the effect of low birth weight (LBW) and fetal anaemia (FA) on haemoglobin (Hb) patterns in infancy. To study the additional contribution of other risk factors known at birth. To examine the effect of iron supplementation during infancy on Hb levels. METHODS: A stratified cohort of infants in Malawi (83 with LBW (< 2500 g), 111 with FA (cord Hb < 125 g/l), 31 with both LBW and FA, and 176 controls) was followed during infancy. Hb levels were measured at about 2, 4, 6, 9, and 12 months of age. Repeated measures models were used to describe the changes in Hb levels over time. RESULTS: The mean Hb concentration in the control group was 95.5 g/l (95% confidence interval (CI) 92.5 to 98.5) at 2 months, 86.9 g/l (95% CI 84.4 to 89.4) at 9 months, and 898 g/l (95% CI 874 to 92.2) at 12 months. Differences between LBW infants and controls increased over time (difference at 12 months: 5.5 g/l (95% CI 1.3 to 9.7)). Infants with FA had borderline significantly lower Hb at 2 months (p = 0.07), but at 6 months their levels were similar to those of controls. The LBW infants and those with FA had the lowest Hb levels (difference from controls at 12 months 7.9 g/l). Parity, placental and maternal malaria at delivery, and sex significantly affected Hb levels after adjustment for LBW and FA. After iron supplementation, Hb significantly increased. CONCLUSIONS: Antimalarial control and iron supplementation throughout pregnancy should be increased to reduce the incidence of infant anaemia and improve child development and survival.