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Rationale: Contacts of patients with tuberculosis (TB) constitute an important target population for preventive measures because they are at high risk of infection with Mycobacterium tuberculosis and progression to disease.Objectives: We investigated biosignatures with predictive ability for incident TB.Methods: In a case-control study nested within the Grand Challenges 6-74 longitudinal HIV-negative African cohort of exposed household contacts, we employed RNA sequencing, PCR, and the pair ratio algorithm in a training/test set approach. Overall, 79 progressors who developed TB between 3 and 24 months after diagnosis of index case and 328 matched nonprogressors who remained healthy during 24 months of follow-up were investigated.Measurements and Main Results: A four-transcript signature derived from samples in a South African and Gambian training set predicted progression up to two years before onset of disease in blinded test set samples from South Africa, the Gambia, and Ethiopia with little population-associated variability, and it was also validated in an external cohort of South African adolescents with latent M. tuberculosis infection. By contrast, published diagnostic or prognostic TB signatures were predicted in samples from some but not all three countries, indicating site-specific variability. Post hoc meta-analysis identified a single gene pair, C1QC/TRAV27 (complement C1q C-chain / T-cell receptor-α variable gene 27) that would consistently predict TB progression in household contacts from multiple African sites but not in infected adolescents without known recent exposure events.Conclusions: Collectively, we developed a simple whole blood-based PCR test to predict TB in recently exposed household contacts from diverse African populations. This test has potential for implementation in national TB contact investigation programs.

Problem With limited global supplies of oral cholera vaccine, countries need to identify priority areas for vaccination while longer-term solutions, such as water and sanitation infrastructure, are being developed. Approach In 2017, Malawi integrated oral cholera vaccine into its national cholera control plan. The process started with a desk review and analysis of previous surveillance and risk factor data. At a consultative meeting, researchers, national health and water officials and representatives from nongovernmental and International organizations reviewed the data and local epidemiological knowledge to determine priority districts for oral cholera vaccination. The final stage was preparation of an application to the global oral cholera vaccine stockpile for non-emergency use. Local setting Malawi collects annual data on cholera and most districts have reported cases at least once since the 1970s. Relevant changes The government's application for 3.2 million doses of vaccine to be provided over 20 months in 12 districts was accepted in April 2017. By April 2018, over 1 million doses had been administered in five districts. Continuing surveillance in districts showed that cholera outbreaks were notably absent in vaccinated high-risk areas, despite a national outbreak in 2017-2018. Lessons learnt Augmenting advanced mapping techniques with local information helped us extend priority areas beyond those identified as high-risk based on cholera Incidence reported at the district level. Involvement of the water, sanitation and hygiene sectors is key to ensuring that short-term gains from cholera vaccine are backed by longer-term progress in reducing cholera transmission. Probleme En raison de stocks mondiaux reduits de vaccins anticholeriques oraux, les pays doivent identifier les zones prioritaires en matiere de vaccination tout en developpant des solutions a plus long terme, telles que des infrastructures d'alimentation en eau et d'assainissement. Approche En 2017, le Malawi a integre la vaccination anticholerique orale dans son plan national de lutte contre le cholera. Le processus a commence par un examen documentaire et une analyse des donnees disponibles concernant la surveillance et les facteurs de risque. Lors d'une reunion consultative, des chercheurs, les responsables nationaux des secteurs de la sante et de l'eau et les representants d'organisations non gouvernementales et internationales ont examine les donnees et les connaissances epidemiologiques locales pour determiner les districts oU devait etre pratiquee en priorite la vaccination anticholerique orale. L'etape finale a consiste a preparer une demande relative au stock mondial de vaccins anticholeriques oraux destines a etre utilises en dehors des situations d'urgence. Environnement local Le Malawi collecte des donnees annuelles sur le cholera et la plupart des districts ont signale des cas a au moins une reprise depuis les annees 1970. Changements significatifs La demande du gouvernement visant la fourniture de 3,2 millions de doses de vaccins pendant 20 mois dans 12 districts a ete acceptee en avril 2017. En avril 2018, plus d'un million de doses ont ete distribuees dans cinq districts. Une surveillance continue au sein des districts a revele un fait frappant, a savoir que les zones a risque epidemlologique eleve ayant fait l'objet d'une vaccination n'ont pas ete touchees par des epidemies de cholera, malgre une epidemie nationale en 2017-2018. Lecons tirees L'association de techniques avancees de cartographie a des informations locales nous a permis d'elargir les zones prioritaires audela de celles identifiees comme presentant un risque epidemiologique eleve en fonction de l'incidence du cholera signalee au niveau des districts. La mobilisation des secteurs de l'eau, de l'assainissement et de l'hygiene est essentielle pour garantir que les avantages a court terme des vaccins anticholeriques sont confirmes par un recul a plus long terme de la transmission du cholera. Problema Con suministros mundiales limitados de la vacuna oral contra el colera, los paises deben identificar las areas prioritarias para la vacunacion mientras se desarrollan soluciones a mas largo plazo, como las infraestructuras de agua y el saneamiento. Enfoque En 2017, Malawi integro la vacuna oral contra el colera en su plan nacional para el control del colera. El proceso empezo con un estudio preliminar y un analisis de los datos previos de vigilancia y factores de riesgo. En una reunion consultiva, investigadores, funcionarios nacionales de salud y agua y representantes de organizaciones no gubernamentales e internacionales revisaron los datos y el conocimiento epidemiologico local para determinar los distritos prioritarios para la vacunacion oral contra el colera. La etapa final fue la preparacion de una aplicacion a la reserva global de la vacuna oral contra el colera para usos de no emergencia. Marco regional Malawi recopila datos anuales sobre el colera y la mayoria de los distritos han registrado casos al menos una vez desde los anos setenta. Cambios importantes La solicitud del gobierno de 3,2 millones de dosis de vacunas para suministrarlas a lo largo de 20 meses en 12 distritos se acepto en abril de 2017. En abril de 2018, se habian administrado mas de 1 millon de dosis en cinco distritos. La vigilancia constante en los distritos mostro que los brotes de colera estuvieron notablemente ausentes en las areas vacunadas de alto riesgo, a pesar de un brote nacional en 2017-2018. Lecciones aprendidas El aumento de las tecnicas avanzadas de mapeo con informacion local ayudo a ampliar las areas prioritarias mas alla de las identificadas como de alto riesgo segun la incidencia del colera registrada a nivel de distrito. La participacion de los sectores del agua, el saneamiento y la higiene es clave para garantizar que las victorias a corto plazo de la vacuna contra el colera esten respaldadas por un progreso a mas largo plazo en la reduccion de la transmision del colera., Introduction Cholera continues to be a global public health threat, with 150 000 cases per year reported from sub-Saharan Africa. (1) While universal access to safe water and sanitation is [...]

Objective To investigate a method of using patient-held records to collect contraception data in Malawi, that could be used to explore contraceptive discontinuation and method switching. Methods In 2012, all 7393 women aged 15 to 49 years living in the area covered by the Karonga demographic surveillance site were offered a family planning card, which was attached to the woman's health passport--a patient-held medical record. Health-care providers were trained to use the cards to record details of contraception given to women. During the study, providers underwent refresher training sessions and received motivational text messages to improve data completeness. After one year, the family planning cards were collected for analysis. Findings Of the 7393 eligible women, 6861 (92.8%) received a family planning card and 4678 (63.3%) returned it after one year. Details of 87.3% (2725/3122) of contacts between health-care providers and the women had been recorded by health-care providers on either family planning cards or health passports. Lower-level health-care providers were more diligent at recording data on the family planning cards than higher-level providers. Conclusion The use of family planning cards was an effective way of recording details of contraception provided by family planning providers. The Involvement of health-care providers was key to the success of this approach. Data collected in this way should prove helpful in producing accurate estimates of method switching and the continuity of contraceptive use by women. [TEXT NOT REPRODUCIBLE IN ASCII] Objectif Examiner une methode consistant a utiliser les dossiers tenus par les patients pour recueillir des donnees sur la contraception au Malawi qui pourraient permettre d'analyser les interruptions et les changements de methodes de contraception. Methodes En 2012, l'ensemble des 7393 femmes agees de 15 a 49 ans de la region couverte par le systeme de surveillance demographique de Karonga s'est vu proposer une carte de planification familiale, attachee a leur carnet de sante--un dossier medical tenu par les patients. Les professionnels de sante ont ete formes a utiliser ces cartes pour noter les renseignements sur la contraception prescrite aux femmes. Au cours de l'etude, ils ont assiste a des seances de remise a niveau et ont recu des SMS d'incitation en vue d'ameliorer l'exhaustivite des renseignements inscrits. Au bout d'un an, les cartes de planification familiale ont ete recueillies pour analyse. Resultats Sur les 7393 femmes eligibles, 6861 (92,8%) ont recu une carte de planification familiale et 4678 (63,3%) l'ont restituee au bout d'un an. Des renseignements sur 87,3% (2725/3122) des contacts entre les professionnels de sante et les femmes avalent ete consignes par les professionnels de sante sur les cartes de planification familiale ou les carnets de sante. Les professionnels de sante de niveau Inferieur etaient plus appliques a inscrire les renseignements sur les cartes de planification familiale que ceux de niveau plus eleve. Conclusion L'utilisation de cartes de planification familiale s'est revelee un moyen efficace de consigner les renseignements sur la contraception prescrite par les prestataires de services de planification familiale. L'implication des professionnels de sante etait indispensable a la reussite de cette demarche. Les donnees recueillies de cette maniere devraient permettre de faire des estimations precises des changements de methodes et de la continuite du recours aux contraceptifs par les femmes. [TEXT NOT REPRODUCIBLE IN ASCII] Objetivo Investigar un metodo para hacer uso de las historias clinicas de los pacientes para recopilar datos sobre los anticonceptivos en Malawi, los cuales podrian utilizarse para estudiar la eliminacion de los anticonceptivos y los cambios de metodos. Metodos En 2012, se ofrecio a todas las 7.393 mujeres de entre 15 y 49 anos que vivian en la zona cubierta por los puestos de vigilancia demografica de Karonga una cartilla de planificacion familiar, que se adjuntaba a su pasaporte sanitario (la historia clinica del paciente). -Se enseno a los profesionales sanitarios a hacer uso de las historias para documentar detalles sobre los anticonceptivos administrados a las mujeres. A lo largo del estudio, los profesionales se sometieron a sesiones formativas de actualizacion y recibieron mensajes de texto motivacionales para mejorar el cumplimiento total de los datos. Despues de un ano, se recogieron las cartillas de planificacion familiar para analizarlas. Resultados De las 7.393 mujeres que cumplian los requisitos, 6.861 (92,8%) recibieron una cartilla de planificacion familiar y 4.678 (63,3%) la devolvieron al cabo de un ano. Los detalles del 87,3% (2.725/3.122) de las visitas entre los profesionales sanitarios y las mujeres fueron documentados por los primeros en las cartillas de planificacion familiar o bien en los pasaportes sanitarios. Los proveedores de atencion sanitaria de bajo rango fueron mas minuciosos a la hora de documentar los datos en las cartillas de planificacion familiar que los de alto rango. Conclusion El uso de las cartillas de planificacion familiarfue una forma efectiva de registrar los detalles de los anticonceptivos administrados por los proveedores de planificacion familiar. La implicacion de los proveedores de atencion sanitaria fue clave para el exito de este enfoque. La informacion recopilada de esta forma debera ser de ayuda a la hora de producir estimaciones rigurosas sobre si existen cambios de metodos y continuidad en el uso de anticonceptivos por parte de las mujeres., Introduction Access to contraceptive services is important, not only because of the direct effect on reproductive health, but also because contraceptive use may lead to indirect improvements in general health [...]

The study attempts to evaluate the association, if any, between CISH polymorphisms and the susceptibility to infectious diseases. The results indicate that variants of CISH are associated with susceptibility to infectious disease and the overall risk of an infectious disease rose by nearly 18% in those carrying the variant CISH alleles.

A study was conducted to evaluate the efficacy and safety of the human rotavirus vaccine in African children suffering from severe diarrhea. Results indicated that the vaccine significantly reduce the incidence of severe rotavirus gastroenteritis among African children.

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 [...]

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 [...]

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, [...]

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. [...]

Abstract 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.

Abstract Background Rotaviruses are the most important cause of severe acute gastroenteritis worldwide in children 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

Abstract 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