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.

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.

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.

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.

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.

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.

Time-space case clusters of Burkitt's lymphoma in Malawi.

The geographical co-ordinates of 146 cases of Burkitt's lymphoma in Malawi, with date of onset between July 1987 and October 1989, were recorded. Case clusters, pairs of cases, closer together in time and space than would be expected by chance, were discovered, using Knox's method, for children over the age of 8 years, but not for all ages.

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.

The efficacy of antimalarial regimens containing sulfadoxine-pyrimethamine and/or chloroquine in preventing peripheral and placental Plasmodium falciparum infection among pregnant women in Malawi.

To define an effective and deliverable antimalarial regimen for use during pregnancy, pregnant women at highest risk of malaria (those in their first or second pregnancy) in an area of Malawi with high transmission of chloroquine (CQ)-resistant Plasmodium falciparum were placed on CQ and/or sulfadoxine-pyrimethamine (SP). Of 38 pregnant women who received CQ treatment followed by weekly CQ prophylaxis (CQ/CQ) for at least 45 days prior to delivery, 32% had placental malaria infection, compared with 26% of 50 pregnant women who received a treatment dose of SP followed by weekly CQ prophylaxis (SP/CQ), and only 9% of 71 pregnant women who received a two-dose SP regimen (SP/SP; given once during the second trimester and repeated at the beginning of the third trimester) (P = 0.006, by chi-square test). During the peak transmission season from April to July, 47% of the women who received CQ/CQ had placental malaria infection at delivery, as compared with 37% of the women who received SP/CQ, and 10% of women who received SP/SP (P = 0.004, by chi-square test). Among women in their first or second pregnancy, two treatment doses of SP were highly effective in decreasing the proportion of women with placental malaria infection at delivery.

Evaluation of maternal practices, efficacy, and cost-effectiveness of alternative antimalarial regimens for use in pregnancy: chloroquine and sulfadoxine-pyrimethamine.

With the knowledge that an efficacious antimalarial administered to pregnant women would markedly reduce placental malaria and its associated risk of low birth weight (LBW), investigations were conducted to identify an antimalarial regimen practical for nationwide implementation through the antenatal clinic (ANC) system. Maternal practices, including ANC utilization and malaria treatment and prevention during pregnancy were evaluated as part of a national malaria knowledge, attitudes, and practices survey. A second study was conducted to evaluate the efficacy and cost of selected alternative antimalarial regimens. Women in their first or second pregnancy were placed on chloroquine (CQ) treatment (25 mg/kg) followed by weekly CQ (300 mg) (CQ/CQ); sulfadoxine-pyrimethamine (SP) treatment followed by CQ (300 mg weekly) (SP/CQ); or SP treatment during the second trimester and repeated at the beginning of the third trimester (SP/SP). With 87% of women attending ANC two or more times during pregnancy, most pregnant women in Malawi could be reached with an antimalarial intervention. Among 159 women in their first or second pregnancy receiving CQ/CQ, SP/CQ, and SP/SP, placental malaria parasitemia rates were 32%, 26%, and 9%, respectively (P = 0.006, by chi-square test). The SP/SP regimen was also markedly more cost-effective in preventing infant deaths, costing $75 per infant death prevented, compared with $481 for SP/CQ and $542 for CQ/CQ. These investigations suggest that a regimen consisting of two treatment doses of SP during pregnancy is an efficacious and cost-effective intervention to prevent placental malaria, and LBW-associated mortality, that can be delivered to pregnant women through ANCs in settings similar to those found in rural Malawi.

Efficacy of mefloquine and sulfadoxine-pyrimethamine for the treatment of uncomplicated Plasmodium falciparum infection in Machinga District, Malawi, 1998.

In response to the spread of chloroquine-resistant Plasmodium falciparum, Malawi changed its first-line antimalarial drug in 1993 from chloroquine to sulfadoxine-pyrimethamine (SP). Surveillance data has suggested that resistance to SP may be increasing. We compared the efficacy of SP with a potential successor, mefloquine (MQ). By use of a modified World Health Organization in vivo protocol, children infected with P. falciparum were randomized to receive SP (sulfadoxine 25 mg/kg) or MQ (15 mg/kg). We observed combined RII and RIII parasitologic failures of 20.0 and 22.0% in the SP and MQ arms, respectively. Among those in the MQ arm, the relative hazard of failing with a Day 2 drug level < 500 ng/mL was 10.6 times higher than those with levels > or = 500 ng/mL. Given the decreased efficacy of the first-line antimalarial drug and the high failure rates of MQ at this lower dosage, Malawi should consider assessing the efficacy and feasibility of alternative drugs to treat uncomplicated falciparum malaria.

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.

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.

Malaria and human immunodeficiency virus infection among male employees of a sugar estate in Malawi.

In sub-saharan Africa, where malaria is endemic and diagnostic and laboratory services are limited, fever is generally presumed to be due to malaria; however, the proportion of fevers actually related to malaria is unknown in most places. This study was conducted to determine the relationship between fever, malaria parasitaemia and human immunodeficiency virus (HIV) infection. Between February and April 1994, 643 consenting adult male workers of the Sugar Corporation of Malawi (SUCOMA) in Nchalo, Chikwawa District, Malawi were enrolled in a cross-sectional study. Participants underwent routine physical examinations and data were collected on age, axillary temperature, and history of fever or other illness in the 2 weeks before enrollment. Patients with axillary temperature > or = 37.5 degrees C were considered to be febrile. Blood was collected and thick blood films were prepared and examined for the presence of malaria parasites. HIV testing was done using the Wellcozyme enzyme-linked immunosorbent assay. Complete information was obtained from 605 subjects (94%), of whom 248 (41%) reported a history of fever (only 15% of the fever reporters were parasitaemic), 139 (23%) were HIV positive, and 131 (22%) received an antimalarial drug. HIV infection was significantly associated with fever but not with parasitaemia. Fever reporters and non-fever reporters were of similar age (means 32.8 and 33.1 years, respectively). These data suggest that in this population there was both high HIV seroprevalence and gross overestimation of fever as malaria. High HIV prevalence makes it necessary to re-examine the common practice in Malawi of treating all fever among adults as malaria.

PIP: 643 adult male employees of the Sugar Corporation of Malawi in Nchalo, Chikwawa District, participated in a cross-sectional study during February-April 1994 to determine the relationship between fever, malaria parasitemia, and HIV infection. Participants underwent routine physical examinations and data were collected on their ages, axillary temperatures, and histories of fever or other illnesses in the 2 weeks before enrollment in the study. Blood was collected and thick blood films prepared and examined for the presence of malaria parasites. Complete information was obtained from 605 subjects, of whom 248 (41%) reported a history of fever, 139 (23%) were HIV positive, and 131 (22%) received an antimalarial drug. Only 15% of fever reporters were parasitemic. HIV infection was significantly associated with fever, but not with parasitemia. Fever reporters and non-fever reporters were of mean ages 32.8 and 33.1 years, respectively. These data suggest that there was both high HIV seroprevalence and considerable overestimation of fever as malaria in this population. This high prevalence of HIV demands the reconsideration of the common practice in Malawi of treating all fever among adults as malaria.

An analysis of intra-uterine growth retardation in rural Malawi.

OBJECTIVE: (1) To describe the sex-specific, birth weight distribution by gestational age of babies born in a malaria endemic, rural area with high maternal HIV prevalence; (2) to assess the contribution of maternal health, nutritional status and obstetric history on intra-uterine growth retardation (IUGR) and prematurity. METHODS: Information was collected on all women attending antenatal services in two hospitals in Chikwawa District, Malawi, and at delivery if at the hospital facilities. Newborns were weighed and gestational age was assessed through post-natal examination (modified Ballard). Sex-specific growth curves were calculated using the LMS method and compared with international reference curves. RESULTS: A total of 1423 live-born singleton babies were enrolled; 14.9% had a birth weight <2500 g, 17.3% were premature (<37 weeks) and 20.3% had IUGR. A fall-off in Malawian growth percentile values occurred between 34 and 37 weeks gestation. Significantly associated with increased IUGR risk were primiparity relative risk (RR) 1.9; 95% CI 1.4--2.6), short maternal stature (RR 1.6; 95% CI 1.0--2.4), anaemia (Hb<8 g/dl) at first antenatal visit (RR 1.6; 95% CI 1.2--2.2) and malaria at delivery (RR 1.4; 95% CI 1.0--1.9). Prematurity risk was associated with primiparity (RR 1.7; 95% CI 1.3--2.4), number of antenatal visits (RR 2.2; 95% CI 1.6--2.9) and arm circumference <23 cm (RR 1.9; 95% CI 1.4--2.5). HIV infection was not associated with IUGR or prematurity. CONCLUSION: The birth-weight-for-gestational-age, sex-specific growth curves should facilitate improved growth monitoring of newborns in African areas where low birth weight and IUGR are common. The prevention of IUGR requires improved malaria control, possibly until late in pregnancy, and reduction of anaemia.

Seroprevalence of hepatitis B and C and HIV in Malawian pregnant women.

OBJECTIVES: to describe the seroprevalence of hepatitis B (HBV) and C (HCV) infection in HIV-positive and HIV-negative pregnant women from rural Malawi. METHODS: descriptive study using serum samples collected between 1993-1995 in the Shire valley in rural Malawi. Fifty HIV-positive and 100 HIV-negative samples were selected randomly from 153 HIV-positive and 443 HIV-negative women delivering in the hospital. RESULTS: evidence of HBV and HCV infection was found in 71.7 and 16.5% of women, respectively. Chronic carriage of HBV (HBsAg positive) is high (13%) and in agreement with prevalences reported from highly endemic areas. Exposure to HBV and HCV probably occurred well before adulthood as the prevalence of anti-HBc antibody was high in young mothers <20 years of age (22/27; 81%). CONCLUSION: HBV and HCV infections are highly endemic in rural Malawi. There was no statistical evidence to suggest that HIV positivity was associated with an increased prevalence of HBV or HCV markers. Infection with HBV or HCV was not statistically associated.

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.

Seasonal variation in the etiology of bloodstream infections in a febrile inpatient population in a developing country.

OBJECTIVES: Published data suggest that Streptococcus pneumoniae, non-typhi Salmonella species, and Mycobacterium tuberculosis are the predominant causes of bloodstream infection (BSI) in hospitalized populations in sub-Saharan Africa. This study was conducted during the wet season to ascertain the etiology and prevalence of BSI among febrile inpatients in a hospital where the dry season BSI profile in a similar study population had already been documented. METHODS: In the period from March to May 1998, consecutive febrile (> or = 37.5 degrees C) adult (> or = 14 y) patients presenting to a Malawi hospital were enrolled after providing informed consent. Following clinical evaluation, blood was drawn for culture (bacteria, mycobacteria, and fungi), human immunodeficiency virus (HIV) testing, and malaria smears. RESULTS: Of 238 enrolled patients, 173 (73%) were HIV-positive and 67 (28%) had BSI. The predominant wet season BSI pathogens were non-typhi Salmonella species (41%), M. tuberculosis (19%), and Cryptococcus neoformans (9%) (cf. the predominant dry season pathogen was S. pneumoniae). Mycobacteremia was more likely in HIV-positive than in HIV-negative patients (13/173 vs. 0/65; P < 0.05). A logistic regression model yielded clinical predictors of BSI that included chronic fever, oral candidiasis, or acute diarrhea. CONCLUSION: Pathogens causing BSI in febrile inpatients in a Malawi teaching hospital vary by season. Season- and country-specific studies, such as this one, provide data that may facilitate empirical therapy of febrile illnesses whose etiologies vary by season.

A study of the consequences of malarial infection in pregnant women and their infants.

An outline is given of a field research study to be undertaken in Malawi to investigate the pattern and consequences of malaria in pregnancy and infants. The central question to be investigated is whether babies born to anaemic mothers in malarious areas are at increased risk of developing anaemia or altered risk for morbidity from malaria or develop anaemia in the first year of life. The framework for the case control and cohort study to be undertaken is outlined.

PIP: Outlined is the protocol for field research in Malawi aimed at ascertaining whether infants born to anemic mothers in areas where malaria is prevalent are at increased risk of morbidity. Specifically, the research seeks to: 1) quantify the prevalence and pattern of anemia in infants living in areas where malaria is endemic; 2) investigate whether birth hemoglobin is associated with clinical risk in infancy; 3) measure the associations between fetal anemia, maternal iron status, and malaria in pregnancy; and 4) quantify the contribution of maternal anemia and iron status to fetal growth retardation. Anemia incidence and malaria prevalence will be assessed through a larger cohort study of infants enrolled at birth and followed for up to 18 months. Also planned is a case-control study that will compare infants born with and without fetal anemia. Odds ratios for maternal anemia, iron deficiency, and parasitemia will be computed for cases and controls to determine the relative contribution of each to fetal hemoglobin status. Finally, the risk of maternal parasitemia, iron deficiency, and anemia will be measured in low-birth-weight, growth-retarded infants and those with normal birth weights. The findings will be used to develop a strategy for anemia control among high risk mothers and infants. This is of particular concern in developing countries, where blood transfusions for anemia can lead to human immunodeficiency virus infection.