This study has demonstrated that preventive therapy with either twice weekly isoniazid for 6 months or a combination of rifampicin and pyrazinamide for 3 months reduced the incidence of TB in HIV-infected persons in Zambia. No effect was observed on mortality. The effect was greatest in persons who had a positive TST or a lymphocyte count of 2x10(9)/l or greater, indicating that preventive therapy may be more effective in people with less advanced immunosuppression. The limited duration of the protective effect reported in this study raises the question of the need for lifelong preventive therapy or re-prophylaxis.

Background Typhoid fever caused by multidrug-resistant H58 Salmonella Typhi is an increasing public-health threat in sub-Saharan Africa. We present phase 3 efficacy data from an African trial of a Vi-polysaccharide typhoid conjugate vaccine (Vi-TCV). Methods Children aged 9 months to 12 years in Blantyre, Malawi were randomized (1:1) in a double-blind trial to receive Vi-TCV (single dose) or group-A meningococcal control vaccine (MenA).The primary outcome was blood culture-confirmed typhoid fever. We present the primary vaccine efficacy (VE) and safety outcomes after 18–24 months of follow-up. Results This intention-to-treat (ITT) analysis included 28,130 children, comprising 14,069 children who received Vi-TCV and 14,061 children who received MenA. Blood culture-confirmed typhoid fever occurred in 12 children in the Vi-TCV group (46.9 per 100,000 person-years) and 62 children in the MenA group (243 per 100,000 person-years). Overall VE was 80.7% (95% confidence interval (CI): 64.2% to 89.6%) in an ITT analysis, and 83.7% (95% CI: 68.1%−91.6%) in a per-protocol analysis. In total, 130 serious adverse events occurred in the first 6 months after vaccination (52 in Vi-TCV group and 78 in MenA group), including 6 deaths (all in MenA group). No serious adverse event was considered by the investigator as related to study vaccination. Conclusions Vi-TCV reduced blood culture-confirmed typhoid fever among Malawian children aged 9 months to 12 years. (Funded by the Bill & Melinda Gates Foundation; ClinicalTrials.gov number NCT03299426 .)

We conducted a clinical study of pregnant women in Blantyre, Malawi to determine the effect of the timing of malaria infection during pregnancy on maternal, infant and placental outcomes. Women were enrolled in their first or second trimester of their first or second pregnancy and followed every four weeks until delivery. Three doses of sulfadoxine-pyrimethamine were given for intermittent preventive treatment for malaria, and all episodes of parasitemia were treated according to the national guidelines. Placentas were collected at delivery and examined for malaria parasites and pigment by histology. Pregnant women had 0.6 episodes of malaria per person year of follow up. Almost all episodes of malaria were detected at enrollment and malaria infection during the follow up period was rare. Malaria and anemia at the first antenatal visit were independently associated with an increased risk of placental malaria detected at delivery. When all episodes of malaria were treated with effective antimalarial medication, only peripheral malaria infection at the time of delivery was associated with adverse maternal and infant outcomes. One quarter of the analyzed placentas had evidence of malaria infection. Placental histology was 78% sensitive and 89% specific for peripheral malaria infection during pregnancy. This study suggests that in this setting of high antifolate drug resistance, three doses of sulfadoxine-pyrimethamine maintain some efficacy in suppressing microscopically detectable parasitemia, although placental infection remains frequent. Even in this urban setting, a large proportion of women have malaria infection at the time of their first antenatal care visit. Interventions to control malaria early and aggressive case detection are required to limit the detrimental effects of pregnancy-associated malaria.

BackgroundMalaria during pregnancy is associated with an increased risk for low birth weight (<2500 grams). Distinguishing infants that are born premature (< 37 weeks) from those that are growth-restricted (less than the 10th percentile at birth) requires accurate assessment of gestational age. Where ultrasound is accessible, sonographic confirmation of gestational age is more accurate than menstrual dating. The goal was to pilot the feasibility and utility of adding ultrasound to an observational pregnancy malaria cohort.MethodsIn July 2009, research staff (three mid-level clinical providers, one nurse) from The Blantyre Malaria Project underwent an intensive one-week ultrasound training to perform foetal biometry. Following an additional four months of practice and remote image review, subjects from an ongoing cohort were recruited for ultrasound to determine gestational age. Gestational age at delivery established by ultrasound was compared with postnatal gestational age assessment (Ballard examination).ResultsOne hundred and seventy-eight women were enrolled. The majority of images were of good quality (94.3%, 509/540) although a learning curve was apparent with 17.5% (24/135) images of unacceptable quality in the first 25% of scans. Ultrasound was used to date 13% of the pregnancies when menstrual dates were unknown and changed the estimated gestational age for an additional 25%. There was poor agreement between the gestational age at delivery as established by the ultrasound protocol compared to that determined by the Ballard examination (bias 0.8 weeks, limits of agreement -3.5 weeks to 5.1 weeks). The distribution of gestational ages by Ballard suggested a clustering of gestational age around the mean with 87% of the values falling between 39 and 41 weeks. The distribution of gestational age by ultrasound confirmed menstrual dates was more typical. Using ultrasound confirmed dates as the gold standard, 78.5% of preterm infants were misclassified as term and 26.8% of small-for gestational age infants misclassified as appropriately grown by Ballard.ConclusionUltrasound should be strongly considered in prospective malaria studies with obstetric endpoints to confirm gestational age and avoid misclassification of infants as premature or growth-restricted. The use of ultrasound does require a significant investment of time to maintain quality image acquisition.

US National Institutes of Health.

Abstract. Pregnant women with influenza infection are at increased risk of developing complications compared with other adults. Information about burden of influenza in pregnant women in Africa is limited. To determine incidence and seasonality of influenza-like illness (ILI) in pregnant women in Blantyre, Malawi, we recruited a cohort of 450 pregnant women and conducted surveillance for ILI and malaria infection. We recorded gestational age and birthweight. We accrued 157 person-years of observation (PYO) and detected 37 episodes of ILI (24/100 PYO) and 83 episodes of malaria infection (including all new episodes of parasitemia) (53/100 PYO). ILI was the most common cause of fever, but was not associated with adverse pregnancy outcomes. ILI incidence peaked during the hot dry season. These results indicate that ILI is a significant burden among Malawian pregnant women and it is somewhat seasonal. Studies with molecular diagnostics are needed to establish influenza-specific burden and the potential role of vaccination.Seasonal influenza carries a large burden of morbidity and mortality throughout the world. Globally, the estimated annual attack rate in adults is 10% and results in 5 million cases of severe illnesses and 500,000 deaths.

BackgroundThe predominance of chloroquine-susceptible falciparum malaria in Malawi more than a decade after chloroquine's withdrawal permits contemplation of re-introducing chloroquine for targeted uses. We aimed to compare the ability of different partner drugs to preserve chloroquine efficacy and prevent the re-emergence of resistance.Methodology/Principal FindingsChildren with uncomplicated malaria were enrolled at a government health center in Blantyre, Malawi. Participants were randomized to receive chloroquine alone or combined with artesunate, azithromycin or atovaquone-proguanil for all episodes of uncomplicated malaria for one year. The primary outcome was incidence of clinical malaria. Secondary endpoints included treatment efficacy, and incidence of the chloroquine resistance marker pfcrt T76 and of anemia. Of the 640 children enrolled, 628 were included in the intention-to-treat analysis. Malaria incidence (95% confidence interval) was 0.59 (.46–.74), .61 (.49–.76), .63 (.50–.79) and .68 (.54–.86) episodes/person-year for group randomized to receive chloroquine alone or in combination with artesunate, azithromycin or atovaquone-proguanil respectively and the differences were not statistically significant. Treatment efficacy for first episodes was 100% for chloroquine monotherapy and 97.9% for subsequent episodes of malaria. Similar results were seen in each of the chloroquine combination groups. The incidence of pfcrt T76 in pure form was 0%; mixed infections with both K76 and T76 were found in two out of 911 infections. Young children treated with chloroquine-azithromycin had higher hemoglobin concentrations at the study's end than did those in the chloroquine monotherapy group.Conclusion/SignificanceSustained chloroquine efficacy with repeated treatment supports the eventual re-introduction of chloroquine combinations for targeted uses such as intermittent preventive treatment.Trial Registration:ClinicalTrials.gov NCT00379821

A simple score incorporating age, ART duration and adherence, and CD4 count can accurately identify adults at low risk for VF in a sub-Saharan African setting. In areas with high ART utilisation and limited VL testing capacity, a targeted approach could optimise routine VL monitoring while identifying adults in need of alternate ART regimens.